chr3-29739836-A-G

Variant names:

• chr3-29739836-A-G
• rs143981652
• NM_001003793.3:c.516A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001003793.3(RBMS3):​c.516A>G​(p.Leu172Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,612,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: RBMS3 NM_001003793.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.456
• Publications: 1 publications found

Genes affected

RBMS3 (HGNC:13427): (RNA binding motif single stranded interacting protein 3) This gene encodes an RNA-binding protein that belongs to the c-myc gene single-strand binding protein family. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. The encoded protein was isolated by virtue of its binding to an upstream element of the alpha2(I) collagen promoter. The observation that this protein localizes mostly in the cytoplasm suggests that it may be involved in a cytoplasmic function such as controlling RNA metabolism, rather than transcription. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

ENSG00000283563 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 3-29739836-A-G is Benign according to our data. Variant chr3-29739836-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 777963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.456 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS3	NM_001003793.3	c.516A>G	p.Leu172Leu	synonymous_variant	Exon 5 of 15	ENST00000383767.7	NP_001003793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7	c.516A>G	p.Leu172Leu	synonymous_variant	Exon 5 of 15	1	NM_001003793.3	ENSP00000373277.2
ENSG00000283563	ENST00000635992.1	n.*1023A>G		non_coding_transcript_exon_variant	Exon 12 of 14	5		ENSP00000489994.1
ENSG00000283563	ENST00000635992.1	n.*1023A>G		3_prime_UTR_variant	Exon 12 of 14	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000609 AC: 152 AN: 249738 AF XY: 0.000526

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000235

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.000658

GnomAD4 exome AF: 0.00114 AC: 1660 AN: 1460148 Hom.: 0 Cov.: 30 AF XY: 0.00110 AC XY: 802 AN XY: 726360

African (AFR) AF: 0.000210 AC: 7 AN: 33406

American (AMR) AF: 0.000158 AC: 7 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 85872

European-Finnish (FIN) AF: 0.000525 AC: 28 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00143 AC: 1584 AN: 1111328

Other (OTH) AF: 0.000547 AC: 33 AN: 60324

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40 AN XY: 74482

African (AFR) AF: 0.000313 AC: 13 AN: 41562

American (AMR) AF: 0.000196 AC: 3 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000956 Hom.: 0

Bravo AF: 0.000555

EpiCase AF: 0.00121

EpiControl AF: 0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.0
DANN	Benign	0.53
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs143981652; hg19: chr3-29781327;