NM_000967.4:c.366-70C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_000967.4(RPL3):c.366-70C>T variant causes a intron change. The variant allele was found at a frequency of 0.00819 in 1,607,250 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 72 hom. )

Consequence

RPL3
NM_000967.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.47

Publications

1 publications found

Variant links:

Genes affected

RPL3 (HGNC:10332): (ribosomal protein L3) Ribosomes, the complexes that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L3P family of ribosomal proteins and it is located in the cytoplasm. The protein can bind to the HIV-1 TAR mRNA, and it has been suggested that the protein contributes to tat-mediated transactivation. This gene is co-transcribed with several small nucleolar RNA genes, which are located in several of this gene's introns. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL3 links:

SNORD139 (HGNC:50421): (small nucleolar RNA, C/D box 139) Intronic regions of ribosomal protein genes can harbor noncoding small nucleolar RNAs (snoRNAs), like U86, which are generated during pre-mRNA processing. snoRNAs form part of the small nucleolar ribonucleoprotein particles (snoRNPs) involved in pre-rRNA processing and modification. snoRNAs of the box C/D class, like U86, function in 2-prime-O-ribose methylation of rRNAs (Duga et al., 2000 [PubMed 10684968]).[supplied by OMIM, Mar 2008]

SNORD139 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 22-39316911-G-A is Benign according to our data. Variant chr22-39316911-G-A is described in ClinVar as Benign. ClinVar VariationId is 2653147.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 812 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000967.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL3	NM_000967.4	MANE Select	c.366-70C>T	intron	N/A	NP_000958.1	P39023
RPL3	NM_001033853.2		c.366-70C>T	intron	N/A	NP_001029025.1
SNORD139	NR_000026.1		n.-15C>T	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL3	ENST00000216146.9	TSL:1 MANE Select	c.366-70C>T	intron	N/A	ENSP00000346001.3	P39023
RPL3	ENST00000401609.5	TSL:1	c.210-70C>T	intron	N/A	ENSP00000386101.1	G5E9G0
RPL3	ENST00000465618.5	TSL:1	n.1136C>T	non_coding_transcript_exon	Exon 4 of 10

Frequencies

GnomAD3 genomes

AF:

0.00534

AC:

812

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00853

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00536

AC:

1316

AN:

245644

AF XY:

0.00563

show subpopulations

Gnomad AFR exome

AF:

0.00115

Gnomad AMR exome

AF:

0.00227

Gnomad ASJ exome

AF:

0.00534

Gnomad EAS exome

AF:

0.0000547

Gnomad FIN exome

AF:

0.00741

Gnomad NFE exome

AF:

0.00865

Gnomad OTH exome

AF:

0.00598

GnomAD4 exome

AF:

0.00849

AC:

12349

AN:

1454932

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

5983

AN XY:

724116

show subpopulations

African (AFR)

AF:

0.00153

AC:

AN:

33342

American (AMR)

AF:

0.00240

AC:

107

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00529

AC:

138

AN:

26092

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39664

South Asian (SAS)

AF:

0.000650

AC:

AN:

86096

European-Finnish (FIN)

AF:

0.00646

AC:

338

AN:

52334

Middle Eastern (MID)

AF:

0.00261

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0101

AC:

11172

AN:

1106778

Other (OTH)

AF:

0.00782

AC:

471

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

632

1264

1897

2529

3161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.00533

AC:

812

AN:

152318

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

365

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41580

American (AMR)

AF:

0.00340

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00750

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00688

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00853

AC:

580

AN:

68022

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

121

162

202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00749

Hom.:

Bravo

AF:

0.00526

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

6.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over