chr3-158272190-T-C

Variant names:

• chr3-158272190-T-C
• rs1213048
• NM_001271838.2:c.495-25849T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001271838.2(RSRC1):​c.495-25849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,910 control chromosomes in the GnomAD database, including 17,797 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 (17797 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521
• Publications: 8 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	NM_001271838.2	MANE Select	c.495-25849T>C		intron	N/A	NP_001258767.1	Q96IZ7-1
	RSRC1	NM_016625.4		c.495-25849T>C		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.321-25849T>C		intron	N/A	NP_001258763.1	Q96IZ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	ENST00000611884.5	TSL:5 MANE Select	c.495-25849T>C		intron	N/A	ENSP00000481697.1	Q96IZ7-1
	RSRC1	ENST00000295930.7	TSL:1	c.495-25849T>C		intron	N/A	ENSP00000295930.3	Q96IZ7-1
	RSRC1	ENST00000312179.10	TSL:1	c.321-25849T>C		intron	N/A	ENSP00000308671.6	Q96IZ7-2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72285 AN: 151792 Hom.: 17775 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.529

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: 0.476 AC: 72354 AN: 151910 Hom.: 17797 Cov.: 32 AF XY: 0.479 AC XY: 35528 AN XY: 74228

African (AFR) AF: 0.559 AC: 23158 AN: 41436

American (AMR) AF: 0.446 AC: 6810 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3319 AN: 5152

South Asian (SAS) AF: 0.299 AC: 1443 AN: 4822

European-Finnish (FIN) AF: 0.529 AC: 5579 AN: 10552

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

European-Non Finnish (NFE) AF: 0.421 AC: 28623 AN: 67912

Other (OTH) AF: 0.494 AC: 1040 AN: 2104

Alfa AF: 0.440 Hom.: 40806

Bravo AF: 0.479

Asia WGS AF: 0.442 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.7
DANN	Benign	0.68
PhyloP100		0.52
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: rs1213048; hg19: chr3-157989979;