1-92833636-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000969.5(RPL5):c.165G>A(p.Val55Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,611,662 control chromosomes in the GnomAD database, including 210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 120 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 90 hom. )

Consequence

RPL5
NM_000969.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.166

Publications

3 publications found

Variant links:

Genes affected

RPL5 (HGNC:10360): (ribosomal protein L5) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L18P family of ribosomal proteins and component of the 60S subunit. The encoded protein binds 5S rRNA to form a stable complex called the 5S ribonucleoprotein particle (RNP), which is necessary for the transport of nonribosome-associated cytoplasmic 5S rRNA to the nucleolus for assembly into ribosomes. The encoded protein may also function to inhibit tumorigenesis through the activation of downstream tumor suppressors and the downregulation of oncoprotein expression. Mutations in this gene have been identified in patients with Diamond-Blackfan Anemia (DBA). This gene is co-transcribed with the small nucleolar RNA gene U21, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Mar 2017]

RPL5 links:

DIPK1A (HGNC:32213): (divergent protein kinase domain 1A) This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

DIPK1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 1-92833636-G-A is Benign according to our data. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92833636-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.166 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL5	NM_000969.5 link	c.165G>A	p.Val55Val	synonymous_variant	Exon 3 of 8	ENST00000370321.8	NP_000960.2	P46777A2RUM7
RPL5	NR_146333.1 link	n.294G>A		non_coding_transcript_exon_variant	Exon 3 of 8
DIPK1A	NM_001252273.2 link	c.475-602C>T		intron_variant	Intron 4 of 4		NP_001239202.1	Q5T7M9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL5	ENST00000370321.8 link	c.165G>A	p.Val55Val	synonymous_variant	Exon 3 of 8	1	NM_000969.5	ENSP00000359345.2		P46777

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3170

AN:

152138

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00825

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.00574

AC:

1443

AN:

251208

AF XY:

0.00417

show subpopulations

Gnomad AFR exome

AF:

0.0762

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00224

AC:

3274

AN:

1459406

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1356

AN XY:

726034

show subpopulations

African (AFR)

AF:

0.0758

AC:

2532

AN:

33390

American (AMR)

AF:

0.00452

AC:

202

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.000151

AC:

AN:

86158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.00402

AC:

AN:

4228

European-Non Finnish (NFE)

AF:

0.000181

AC:

201

AN:

1111552

Other (OTH)

AF:

0.00496

AC:

299

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

155

310

465

620

775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0209

AC:

3184

AN:

152256

Hom.:

120

Cov.:

AF XY:

0.0206

AC XY:

1532

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0720

AC:

2992

AN:

41534

American (AMR)

AF:

0.00824

AC:

126

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68022

Other (OTH)

AF:

0.0194

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

153

305

458

610

763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00938

Hom.:

Bravo

AF:

0.0236

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diamond-Blackfan anemia

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Diamond-Blackfan anemia 6

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 28, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 04, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.3

(source)

DANN

Benign

0.85

PhyloP100

0.17

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over