3-158454616-T-C

Variant names:

• chr3-158454616-T-C
• rs10936142
• NM_001271838.2:c.584-6319T>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.584-6319T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,926 control chromosomes in the GnomAD database, including 8,701 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 0.32 (8701 hom., cov: 31)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.584-6319T>C		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.584-6319T>C		intron_variant	Intron 6 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49052 AN: 151810 Hom.: 8703 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.323 AC: 49063 AN: 151926 Hom.: 8701 Cov.: 31 AF XY: 0.324 AC XY: 24041 AN XY: 74268

African (AFR) AF: 0.181 AC: 7491 AN: 41430

American (AMR) AF: 0.398 AC: 6068 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1269 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1053 AN: 5172

South Asian (SAS) AF: 0.462 AC: 2215 AN: 4798

European-Finnish (FIN) AF: 0.303 AC: 3209 AN: 10578

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26659 AN: 67914

Other (OTH) AF: 0.337 AC: 711 AN: 2110

Alfa AF: 0.378 Hom.: 43742

Bravo AF: 0.322

Asia WGS AF: 0.352 AC: 1222 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.64
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: rs10936142; hg19: chr3-158172405;