rs1369562

Variant names:

• chr3-158490771-T-C
• rs1369562
• NM_001271838.2:c.652+29768T>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.652+29768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,060 control chromosomes in the GnomAD database, including 20,796 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 (20796 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.652+29768T>C		intron_variant	Intron 7 of 9	ENST00000611884.5	NP_001258767.1
RSRC1	NM_016625.4	c.652+29768T>C		intron_variant	Intron 7 of 9		NP_057709.2
RSRC1	NM_001271834.2	c.478+29768T>C		intron_variant	Intron 6 of 8		NP_001258763.1
RSRC1	XM_047448275.1	c.652+29768T>C		intron_variant	Intron 7 of 9		XP_047304231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.652+29768T>C		intron_variant	Intron 7 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78463 AN: 151942 Hom.: 20776 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.516 AC: 78530 AN: 152060 Hom.: 20796 Cov.: 32 AF XY: 0.517 AC XY: 38389 AN XY: 74300

African (AFR) AF: 0.628 AC: 26052 AN: 41482

American (AMR) AF: 0.510 AC: 7794 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1484 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1682 AN: 5166

South Asian (SAS) AF: 0.605 AC: 2908 AN: 4808

European-Finnish (FIN) AF: 0.425 AC: 4486 AN: 10554

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32577 AN: 67986

Other (OTH) AF: 0.491 AC: 1036 AN: 2108

Alfa AF: 0.508 Hom.: 3258

Bravo AF: 0.525

Asia WGS AF: 0.515 AC: 1790 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.6
DANN	Benign	0.29
PhyloP100		0.044
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: rs1369562; hg19: chr3-158208560;