NM_001271838.2:c.652+19930A>G

Variant names:

• chr3-158480933-A-G
• rs6769314
• NM_001271838.2:c.652+19930A>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.652+19930A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,996 control chromosomes in the GnomAD database, including 2,115 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 0.16 (2115 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.652+19930A>G		intron_variant	Intron 7 of 9	ENST00000611884.5	NP_001258767.1
RSRC1	NM_016625.4	c.652+19930A>G		intron_variant	Intron 7 of 9		NP_057709.2
RSRC1	NM_001271834.2	c.478+19930A>G		intron_variant	Intron 6 of 8		NP_001258763.1
RSRC1	XM_047448275.1	c.652+19930A>G		intron_variant	Intron 7 of 9		XP_047304231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.652+19930A>G		intron_variant	Intron 7 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24976 AN: 151878 Hom.: 2111 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0985

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.164 AC: 25001 AN: 151996 Hom.: 2115 Cov.: 32 AF XY: 0.165 AC XY: 12234 AN XY: 74304

African (AFR) AF: 0.201 AC: 8360 AN: 41498

American (AMR) AF: 0.183 AC: 2782 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3468

East Asian (EAS) AF: 0.0979 AC: 506 AN: 5166

South Asian (SAS) AF: 0.186 AC: 898 AN: 4816

European-Finnish (FIN) AF: 0.121 AC: 1286 AN: 10598

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10066 AN: 67920

Other (OTH) AF: 0.157 AC: 330 AN: 2108

Alfa AF: 0.157 Hom.: 2678

Bravo AF: 0.170

Asia WGS AF: 0.168 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.61
PhyloP100		-0.83
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: rs6769314; hg19: chr3-158198722;