3-158299208-T-C

Variant names:

• chr3-158299208-T-C
• rs1730007
• NM_001271838.2:c.531+1133T>C

Variant summary

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

The NM_001271838.2(RSRC1):​c.531+1133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,998 control chromosomes in the GnomAD database, including 17,799 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 0.48 (17799 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.531+1133T>C		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.531+1133T>C		intron_variant	Intron 5 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72322 AN: 151880 Hom.: 17777 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.476 AC: 72391 AN: 151998 Hom.: 17799 Cov.: 32 AF XY: 0.479 AC XY: 35555 AN XY: 74290

African (AFR) AF: 0.559 AC: 23174 AN: 41454

American (AMR) AF: 0.446 AC: 6820 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1659 AN: 3470

East Asian (EAS) AF: 0.643 AC: 3328 AN: 5174

South Asian (SAS) AF: 0.300 AC: 1447 AN: 4826

European-Finnish (FIN) AF: 0.530 AC: 5583 AN: 10542

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28609 AN: 67932

Other (OTH) AF: 0.494 AC: 1044 AN: 2112

Alfa AF: 0.447 Hom.: 2490

Bravo AF: 0.479

Asia WGS AF: 0.442 AC: 1535 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.31
DANN	Benign	0.72
PhyloP100		-1.4
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: rs1730007; hg19: chr3-158016997;