rs10936131

Variant names:

• chr3-158353069-C-T
• rs10936131
• NM_001271838.2:c.532-1788C>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.532-1788C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,066 control chromosomes in the GnomAD database, including 4,280 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 0.22 (4280 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.532-1788C>T		intron_variant	Intron 5 of 9	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.532-1788C>T		intron_variant	Intron 5 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33442 AN: 151948 Hom.: 4283 Cov.: 32

Gnomad AFR AF: 0.0978

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.220 AC: 33431 AN: 152066 Hom.: 4280 Cov.: 32 AF XY: 0.218 AC XY: 16231 AN XY: 74328

African (AFR) AF: 0.0976 AC: 4052 AN: 41506

American (AMR) AF: 0.244 AC: 3722 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3468

East Asian (EAS) AF: 0.148 AC: 765 AN: 5164

South Asian (SAS) AF: 0.283 AC: 1361 AN: 4810

European-Finnish (FIN) AF: 0.232 AC: 2441 AN: 10542

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.289 AC: 19665 AN: 67984

Other (OTH) AF: 0.219 AC: 463 AN: 2110

Alfa AF: 0.274 Hom.: 8224

Bravo AF: 0.214

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.49
PhyloP100		-0.57
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: rs10936131; hg19: chr3-158070858;