chr3-158538339-T-C

Variant names:

• chr3-158538339-T-C
• rs16829102
• NM_001271838.2:c.759+1141T>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.759+1141T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,822 control chromosomes in the GnomAD database, including 1,351 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 0.12 (1351 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 7 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.759+1141T>C		intron_variant	Intron 8 of 9	ENST00000611884.5	NP_001258767.1
RSRC1	NM_016625.4	c.759+1141T>C		intron_variant	Intron 8 of 9		NP_057709.2
RSRC1	NM_001271834.2	c.585+1141T>C		intron_variant	Intron 7 of 8		NP_001258763.1
RSRC1	XM_047448275.1	c.759+1141T>C		intron_variant	Intron 8 of 9		XP_047304231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.759+1141T>C		intron_variant	Intron 8 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17725 AN: 151704 Hom.: 1350 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0609

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.117 AC: 17756 AN: 151822 Hom.: 1351 Cov.: 32 AF XY: 0.116 AC XY: 8633 AN XY: 74240

African (AFR) AF: 0.218 AC: 9032 AN: 41466

American (AMR) AF: 0.0838 AC: 1277 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0609 AC: 211 AN: 3464

East Asian (EAS) AF: 0.117 AC: 606 AN: 5166

South Asian (SAS) AF: 0.115 AC: 553 AN: 4822

European-Finnish (FIN) AF: 0.0677 AC: 718 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0754 AC: 5107 AN: 67740

Other (OTH) AF: 0.103 AC: 218 AN: 2108

Alfa AF: 0.0855 Hom.: 431

Bravo AF: 0.123

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		1.2
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: rs16829102; hg19: chr3-158256128;