chr3-158397464-C-A

Variant names:

• chr3-158397464-C-A
• rs939114
• NM_001271838.2:c.583+42556C>A

Variant summary

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

The NM_001271838.2(RSRC1):​c.583+42556C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,954 control chromosomes in the GnomAD database, including 14,706 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 0.43 (14706 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.583 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.583+42556C>A		intron	N/A	NP_001258767.1	Q96IZ7-1
	RSRC1	NM_016625.4		c.583+42556C>A		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.409+42556C>A		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.583+42556C>A		intron	N/A	ENSP00000481697.1	Q96IZ7-1
	RSRC1	ENST00000295930.7	TSL:1	c.583+42556C>A		intron	N/A	ENSP00000295930.3	Q96IZ7-1
	RSRC1	ENST00000312179.10	TSL:1	c.409+42556C>A		intron	N/A	ENSP00000308671.6	Q96IZ7-2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64715 AN: 151834 Hom.: 14707 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.426 AC: 64734 AN: 151954 Hom.: 14706 Cov.: 32 AF XY: 0.426 AC XY: 31621 AN XY: 74252

African (AFR) AF: 0.278 AC: 11521 AN: 41498

American (AMR) AF: 0.492 AC: 7506 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1687 AN: 5156

South Asian (SAS) AF: 0.602 AC: 2898 AN: 4816

European-Finnish (FIN) AF: 0.383 AC: 4046 AN: 10562

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34107 AN: 67896

Other (OTH) AF: 0.430 AC: 907 AN: 2110

Alfa AF: 0.483 Hom.: 57349

Bravo AF: 0.424

Asia WGS AF: 0.490 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.78
PhyloP100		0.25
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: rs939114; hg19: chr3-158115253;