Genetic Variant RPL31:c.*74C>A (chr2-101006165-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001099693.2(RPL31):c.*74C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 1,539,538 control chromosomes in the GnomAD database, including 426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 248 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 178 hom. )

Consequence

RPL31
NM_001099693.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.245

Publications

1 publications found

Variant links:

Genes affected

RPL31 (HGNC:10334): (ribosomal protein L31) Ribosomes, the organelles 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 L31E family of ribosomal proteins. It is located in the cytoplasm. Higher levels of expression of this gene in familial adenomatous polyps compared to matched normal tissues have been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RPL31 links:

TBC1D8 (HGNC:17791): (TBC1 domain family member 8) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-101006165-C-A is Benign according to our data. Variant chr2-101006165-C-A is described in ClinVar as Benign. ClinVar VariationId is 1228799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099693.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL31	NM_000993.5	MANE Select	c.346+94C>A	intron	N/A	NP_000984.1	P62899-1
RPL31	NM_001099693.2		c.*74C>A	3_prime_UTR	Exon 4 of 4	NP_001093163.1	P62899-3
RPL31	NM_001098577.3		c.346+94C>A	intron	N/A	NP_001092047.1	P62899-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL31	ENST00000409320.7	TSL:1	c.*74C>A	3_prime_UTR	Exon 4 of 4	ENSP00000387163.3	P62899-3
RPL31	ENST00000264258.8	TSL:1 MANE Select	c.346+94C>A	intron	N/A	ENSP00000264258.3	P62899-1
RPL31	ENST00000409733.5	TSL:1	c.346+94C>A	intron	N/A	ENSP00000386681.1	P62899-1

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4549

AN:

152156

Hom.:

247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0191

GnomAD4 exome

AF:

0.00313

AC:

4340

AN:

1387264

Hom.:

178

Cov.:

AF XY:

0.00280

AC XY:

1916

AN XY:

684372

show subpopulations

African (AFR)

AF:

0.104

AC:

3153

AN:

30458

American (AMR)

AF:

0.00716

AC:

229

AN:

31992

Ashkenazi Jewish (ASJ)

AF:

0.00139

AC:

AN:

23736

East Asian (EAS)

AF:

0.00

AC:

AN:

36636

South Asian (SAS)

AF:

0.000118

AC:

AN:

76348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49640

Middle Eastern (MID)

AF:

0.00663

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.000443

AC:

476

AN:

1075490

Other (OTH)

AF:

0.00702

AC:

403

AN:

57386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

211

421

632

842

1053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.0299

AC:

4556

AN:

152274

Hom.:

248

Cov.:

AF XY:

0.0291

AC XY:

2170

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.103

AC:

4297

AN:

41534

American (AMR)

AF:

0.0126

AC:

192

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68024

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

190

380

570

760

950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0216

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.1

(source)

DANN

Benign

0.69

PhyloP100

-0.24

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over