3-158291688-A-G

Variant names:

• chr3-158291688-A-G
• rs13066362
• NM_001271838.2:c.495-6351A>G

Variant summary

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

The NM_001271838.2(RSRC1):​c.495-6351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,042 control chromosomes in the GnomAD database, including 12,394 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 0.39 (12394 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 7 publications found

Genes affected

RSRC1 (HGNC:24152): (arginine and serine rich coiled-coil 1) This gene encodes a member of the serine and arginine rich-related protein family. The encoded protein is involved in both constitutive and alternative mRNA splicing. This gene may be associated with schizophrenia. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

RSRC1 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal recessive 70

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.495-6351A>G		intron_variant	Intron 4 of 9	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.495-6351A>G		intron_variant	Intron 4 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59179 AN: 151924 Hom.: 12386 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.389 AC: 59197 AN: 152042 Hom.: 12394 Cov.: 32 AF XY: 0.395 AC XY: 29320 AN XY: 74312

African (AFR) AF: 0.252 AC: 10464 AN: 41506

American (AMR) AF: 0.427 AC: 6526 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3325 AN: 5174

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4820

European-Finnish (FIN) AF: 0.531 AC: 5593 AN: 10540

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28573 AN: 67952

Other (OTH) AF: 0.429 AC: 904 AN: 2106

Alfa AF: 0.394 Hom.: 2105

Bravo AF: 0.381

Asia WGS AF: 0.419 AC: 1445 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		0.27
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: rs13066362; hg19: chr3-158009477;