rs9876322

Variant names:

• chr3-158401449-C-A
• rs9876322
• NM_001271838.2:c.583+46541C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-158401449-C-A
• chr3-158401449-C-T

Variant summary

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

The NM_001271838.2(RSRC1):​c.583+46541C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,626 control chromosomes in the GnomAD database, including 20,942 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 0.52 (20942 hom., cov: 31)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.583+46541C>A		intron_variant	Intron 6 of 9	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.583+46541C>A		intron_variant	Intron 6 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78803 AN: 151506 Hom.: 20918 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.520 AC: 78878 AN: 151626 Hom.: 20942 Cov.: 31 AF XY: 0.517 AC XY: 38274 AN XY: 74072

African (AFR) AF: 0.607 AC: 25140 AN: 41396

American (AMR) AF: 0.518 AC: 7880 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1642 AN: 3466

East Asian (EAS) AF: 0.328 AC: 1694 AN: 5162

South Asian (SAS) AF: 0.603 AC: 2905 AN: 4820

European-Finnish (FIN) AF: 0.384 AC: 4045 AN: 10530

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34099 AN: 67740

Other (OTH) AF: 0.496 AC: 1043 AN: 2102

Alfa AF: 0.453 Hom.: 2449

Bravo AF: 0.530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		0.94
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: rs9876322; hg19: chr3-158119238; COSMIC: COSV55832513;