3-158233092-T-C

Variant names:

• chr3-158233092-T-C
• rs827123
• NM_001271838.2:c.494+29847T>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.494+29847T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,816 control chromosomes in the GnomAD database, including 29,002 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 0.61 (29002 hom., cov: 31)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• Publications: 8 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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.494+29847T>C		intron_variant	Intron 4 of 9	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.494+29847T>C		intron_variant	Intron 4 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93148 AN: 151698 Hom.: 28968 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.614 AC: 93233 AN: 151816 Hom.: 29002 Cov.: 31 AF XY: 0.618 AC XY: 45813 AN XY: 74164

African (AFR) AF: 0.656 AC: 27175 AN: 41436

American (AMR) AF: 0.625 AC: 9526 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2298 AN: 3466

East Asian (EAS) AF: 0.730 AC: 3757 AN: 5148

South Asian (SAS) AF: 0.484 AC: 2331 AN: 4812

European-Finnish (FIN) AF: 0.653 AC: 6878 AN: 10530

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39037 AN: 67886

Other (OTH) AF: 0.643 AC: 1351 AN: 2102

Alfa AF: 0.578 Hom.: 13045

Bravo AF: 0.618

Asia WGS AF: 0.610 AC: 2121 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs827123; hg19: chr3-157950881;