chr3-158217837-A-G

Variant names:

• chr3-158217837-A-G
• rs10513524
• NM_001271838.2:c.494+14592A>G

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+14592A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 151,328 control chromosomes in the GnomAD database, including 548 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 0.077 (548 hom., cov: 30)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• Publications: 3 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	NM_001271838.2	MANE Select	c.494+14592A>G		intron	N/A	NP_001258767.1	Q96IZ7-1
	RSRC1	NM_016625.4		c.494+14592A>G		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.321-80202A>G		intron	N/A	NP_001258763.1	Q96IZ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	ENST00000611884.5	TSL:5 MANE Select	c.494+14592A>G		intron	N/A	ENSP00000481697.1	Q96IZ7-1
	RSRC1	ENST00000295930.7	TSL:1	c.494+14592A>G		intron	N/A	ENSP00000295930.3	Q96IZ7-1
	RSRC1	ENST00000312179.10	TSL:1	c.321-80202A>G		intron	N/A	ENSP00000308671.6	Q96IZ7-2

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11559 AN: 151210 Hom.: 544 Cov.: 30

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0663

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

GnomAD4 genome AF: 0.0765 AC: 11578 AN: 151328 Hom.: 548 Cov.: 30 AF XY: 0.0762 AC XY: 5632 AN XY: 73922

African (AFR) AF: 0.100 AC: 4146 AN: 41260

American (AMR) AF: 0.0776 AC: 1175 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.0871 AC: 301 AN: 3456

East Asian (EAS) AF: 0.112 AC: 569 AN: 5100

South Asian (SAS) AF: 0.129 AC: 622 AN: 4806

European-Finnish (FIN) AF: 0.0310 AC: 327 AN: 10554

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0630 AC: 4263 AN: 67702

Other (OTH) AF: 0.0680 AC: 143 AN: 2102

Alfa AF: 0.0676 Hom.: 635

Bravo AF: 0.0806

Asia WGS AF: 0.131 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.59
PhyloP100		-0.80
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: rs10513524; hg19: chr3-157935626;