3-158408538-T-G

Variant names:

• chr3-158408538-T-G
• rs12107104
• NM_001271838.2:c.584-52397T>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.584-52397T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,902 control chromosomes in the GnomAD database, including 19,320 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 0.50 (19320 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.584-52397T>G		intron_variant	Intron 6 of 9	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.584-52397T>G		intron_variant	Intron 6 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76000 AN: 151784 Hom.: 19311 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.501 AC: 76053 AN: 151902 Hom.: 19320 Cov.: 32 AF XY: 0.498 AC XY: 36932 AN XY: 74212

African (AFR) AF: 0.537 AC: 22252 AN: 41426

American (AMR) AF: 0.513 AC: 7821 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1645 AN: 3470

East Asian (EAS) AF: 0.332 AC: 1712 AN: 5156

South Asian (SAS) AF: 0.603 AC: 2911 AN: 4826

European-Finnish (FIN) AF: 0.384 AC: 4044 AN: 10538

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34226 AN: 67936

Other (OTH) AF: 0.480 AC: 1012 AN: 2110

Alfa AF: 0.503 Hom.: 3335

Bravo AF: 0.508

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		-0.17
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: rs12107104; hg19: chr3-158126327;