3-29654097-T-C

Variant names:

• chr3-29654097-T-C
• rs10510622
• NM_001003793.3:c.399+66892T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003793.3(RBMS3):​c.399+66892T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,128 control chromosomes in the GnomAD database, including 4,429 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4429 hom., cov: 32)
• Consequence: RBMS3 NM_001003793.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS3	NM_001003793.3	c.399+66892T>C		intron_variant	Intron 4 of 14	ENST00000383767.7	NP_001003793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7	c.399+66892T>C		intron_variant	Intron 4 of 14	1	NM_001003793.3	ENSP00000373277.2
ENSG00000283563	ENST00000635992.1	n.*906+66892T>C		intron_variant	Intron 11 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35036 AN: 152010 Hom.: 4426 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.231 AC: 35080 AN: 152128 Hom.: 4429 Cov.: 32 AF XY: 0.231 AC XY: 17200 AN XY: 74376

African (AFR) AF: 0.300 AC: 12439 AN: 41474

American (AMR) AF: 0.283 AC: 4319 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1822 AN: 5166

South Asian (SAS) AF: 0.304 AC: 1468 AN: 4826

European-Finnish (FIN) AF: 0.120 AC: 1276 AN: 10608

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12338 AN: 67990

Other (OTH) AF: 0.244 AC: 515 AN: 2110

Alfa AF: 0.201 Hom.: 12722

Bravo AF: 0.249

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.46
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs10510622; hg19: chr3-29695588;