rs10510614

Variant names:

• chr3-28731344-A-G
• rs10510614
• ENST00000635992.1:n.*340-133880A>G

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*340-133880A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 152,274 control chromosomes in the GnomAD database, including 538 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 0.077 (538 hom., cov: 33)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 1 publications found

Genes affected

ENSG00000283563 (HGNC:):

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]

LINC00693 (HGNC:44526): (long intergenic non-protein coding RNA 693)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC00693	NR_038840.1	n.323-25414A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283563	ENST00000635992.1	n.*340-133880A>G		intron_variant	Intron 6 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11767 AN: 152156 Hom.: 532 Cov.: 33

Gnomad AFR AF: 0.0910

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0460

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0774 AC: 11781 AN: 152274 Hom.: 538 Cov.: 33 AF XY: 0.0798 AC XY: 5940 AN XY: 74462

African (AFR) AF: 0.0910 AC: 3780 AN: 41546

American (AMR) AF: 0.0623 AC: 952 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 322 AN: 3472

East Asian (EAS) AF: 0.155 AC: 805 AN: 5186

South Asian (SAS) AF: 0.175 AC: 843 AN: 4822

European-Finnish (FIN) AF: 0.0460 AC: 489 AN: 10622

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0639 AC: 4346 AN: 68018

Other (OTH) AF: 0.0833 AC: 176 AN: 2114

Alfa AF: 0.0666 Hom.: 134

Bravo AF: 0.0771

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.86
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10510614; hg19: chr3-28772835;