chr3-158261915-C-T

Variant names:

• chr3-158261915-C-T
• rs827113
• NM_001271838.2:c.495-36124C>T

Variant summary

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

The NM_001271838.2(RSRC1):​c.495-36124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,900 control chromosomes in the GnomAD database, including 17,817 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 (17817 hom., cov: 31)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 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.495-36124C>T		intron	N/A	NP_001258767.1
	RSRC1	NM_016625.4		c.495-36124C>T		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.321-36124C>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.495-36124C>T		intron	N/A	ENSP00000481697.1
	RSRC1	ENST00000295930.7	TSL:1	c.495-36124C>T		intron	N/A	ENSP00000295930.3
	RSRC1	ENST00000312179.10	TSL:1	c.321-36124C>T		intron	N/A	ENSP00000308671.6

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72338 AN: 151782 Hom.: 17794 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.477 AC: 72409 AN: 151900 Hom.: 17817 Cov.: 31 AF XY: 0.479 AC XY: 35567 AN XY: 74234

African (AFR) AF: 0.560 AC: 23182 AN: 41430

American (AMR) AF: 0.447 AC: 6814 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3466

East Asian (EAS) AF: 0.645 AC: 3331 AN: 5168

South Asian (SAS) AF: 0.300 AC: 1444 AN: 4816

European-Finnish (FIN) AF: 0.532 AC: 5595 AN: 10526

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

European-Non Finnish (NFE) AF: 0.421 AC: 28625 AN: 67944

Other (OTH) AF: 0.494 AC: 1037 AN: 2098

Alfa AF: 0.445 Hom.: 2629

Bravo AF: 0.479

Asia WGS AF: 0.442 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.25
PhyloP100		-0.75
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: rs827113; hg19: chr3-157979704;