chr3-158309190-A-T

Variant names:

• chr3-158309190-A-T
• rs2693542
• NM_001271838.2:c.531+11115A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001271838.2(RSRC1):​c.531+11115A>T variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,586 control chromosomes in the GnomAD database, including 18,205 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 (18205 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.51
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271838.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	NM_001271838.2	MANE Select	c.531+11115A>T		intron	N/A	NP_001258767.1
	RSRC1	NM_016625.4		c.531+11115A>T		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.357+11115A>T		intron	N/A	NP_001258763.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	ENST00000611884.5	TSL:5 MANE Select	c.531+11115A>T		intron	N/A	ENSP00000481697.1
	RSRC1	ENST00000295930.7	TSL:1	c.531+11115A>T		intron	N/A	ENSP00000295930.3
	RSRC1	ENST00000312179.10	TSL:1	c.357+11115A>T		intron	N/A	ENSP00000308671.6

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72916 AN: 151466 Hom.: 18182 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.481 AC: 72987 AN: 151586 Hom.: 18205 Cov.: 32 AF XY: 0.483 AC XY: 35821 AN XY: 74092

African (AFR) AF: 0.577 AC: 23904 AN: 41400

American (AMR) AF: 0.448 AC: 6810 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1651 AN: 3460

East Asian (EAS) AF: 0.643 AC: 3320 AN: 5162

South Asian (SAS) AF: 0.300 AC: 1441 AN: 4810

European-Finnish (FIN) AF: 0.530 AC: 5592 AN: 10554

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

European-Non Finnish (NFE) AF: 0.421 AC: 28498 AN: 67682

Other (OTH) AF: 0.496 AC: 1045 AN: 2108

Alfa AF: 0.320 Hom.: 812

Bravo AF: 0.485

Asia WGS AF: 0.444 AC: 1544 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.90
PhyloP100		8.5
Mutation Taster		=86/14	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: rs2693542; hg19: chr3-158026979;