3-158488994-G-T

Variant names:

• chr3-158488994-G-T
• rs1978781
• NM_001271838.2:c.652+27991G>T

Variant summary

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

The ENST00000611884.5(RSRC1):​c.652+27991G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,018 control chromosomes in the GnomAD database, including 21,137 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 (21137 hom., cov: 32)
• Consequence: RSRC1 ENST00000611884.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611884.5. 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.652+27991G>T		intron	N/A	NP_001258767.1
	RSRC1	NM_016625.4		c.652+27991G>T		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.478+27991G>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.652+27991G>T		intron	N/A	ENSP00000481697.1
	RSRC1	ENST00000295930.7	TSL:1	c.652+27991G>T		intron	N/A	ENSP00000295930.3
	RSRC1	ENST00000312179.10	TSL:1	c.478+27991G>T		intron	N/A	ENSP00000308671.6

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79048 AN: 151900 Hom.: 21114 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.520 AC: 79119 AN: 152018 Hom.: 21137 Cov.: 32 AF XY: 0.521 AC XY: 38699 AN XY: 74290

African (AFR) AF: 0.641 AC: 26595 AN: 41478

American (AMR) AF: 0.511 AC: 7801 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1484 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1687 AN: 5178

South Asian (SAS) AF: 0.606 AC: 2918 AN: 4818

European-Finnish (FIN) AF: 0.427 AC: 4499 AN: 10540

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32579 AN: 67960

Other (OTH) AF: 0.495 AC: 1045 AN: 2110

Alfa AF: 0.408 Hom.: 1621

Bravo AF: 0.529

Asia WGS AF: 0.514 AC: 1785 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.35
PhyloP100		-0.63
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: rs1978781; hg19: chr3-158206783;