chr3-158354468-A-G

Variant names:

• chr3-158354468-A-G
• rs7610713
• NM_001271838.2:c.532-389A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016625.4(RSRC1):​c.532-389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,986 control chromosomes in the GnomAD database, including 21,159 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 0.52 (21159 hom., cov: 31)
• Consequence: RSRC1 NM_016625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016625.4. 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.532-389A>G		intron	N/A	NP_001258767.1
	RSRC1	NM_016625.4		c.532-389A>G		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.358-389A>G		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.532-389A>G		intron	N/A	ENSP00000481697.1
	RSRC1	ENST00000295930.7	TSL:1	c.532-389A>G		intron	N/A	ENSP00000295930.3
	RSRC1	ENST00000312179.10	TSL:1	c.358-389A>G		intron	N/A	ENSP00000308671.6

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79355 AN: 151868 Hom.: 21135 Cov.: 31

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.523 AC: 79427 AN: 151986 Hom.: 21159 Cov.: 31 AF XY: 0.519 AC XY: 38580 AN XY: 74286

African (AFR) AF: 0.609 AC: 25246 AN: 41426

American (AMR) AF: 0.519 AC: 7933 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1918 AN: 5176

South Asian (SAS) AF: 0.598 AC: 2882 AN: 4820

European-Finnish (FIN) AF: 0.386 AC: 4074 AN: 10550

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.504 AC: 34256 AN: 67950

Other (OTH) AF: 0.497 AC: 1047 AN: 2108

Alfa AF: 0.414 Hom.: 1463

Bravo AF: 0.533

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.75
PhyloP100		-0.33
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: rs7610713; hg19: chr3-158072257;