rs6806967

Variant names:

• chr3-158460456-C-T
• rs6806967
• NM_001271838.2:c.584-479C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001271838.2(RSRC1):​c.584-479C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,650 control chromosomes in the GnomAD database, including 3,049 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 0.19 (3049 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.584-479C>T		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.584-479C>T		intron_variant	Intron 6 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28418 AN: 151532 Hom.: 3051 Cov.: 32

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.187 AC: 28413 AN: 151650 Hom.: 3049 Cov.: 32 AF XY: 0.187 AC XY: 13828 AN XY: 74084

African (AFR) AF: 0.0884 AC: 3667 AN: 41460

American (AMR) AF: 0.224 AC: 3415 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3464

East Asian (EAS) AF: 0.0990 AC: 511 AN: 5162

South Asian (SAS) AF: 0.274 AC: 1317 AN: 4812

European-Finnish (FIN) AF: 0.181 AC: 1910 AN: 10524

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.241 AC: 16305 AN: 67682

Other (OTH) AF: 0.192 AC: 403 AN: 2102

Alfa AF: 0.222 Hom.: 10890

Bravo AF: 0.184

Asia WGS AF: 0.184 AC: 638 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.81
PhyloP100		2.0
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: rs6806967; hg19: chr3-158178245;