3-158347120-T-C

Variant names:

• chr3-158347120-T-C
• rs827135
• NM_001271838.2:c.532-7737T>C

Variant summary

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

The NM_001271838.2(RSRC1):​c.532-7737T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,070 control chromosomes in the GnomAD database, including 13,440 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 0.41 (13440 hom., cov: 33)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 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.532-7737T>C		intron	N/A	NP_001258767.1
	RSRC1	NM_016625.4		c.532-7737T>C		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.358-7737T>C		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.532-7737T>C		intron	N/A	ENSP00000481697.1
	RSRC1	ENST00000295930.7	TSL:1	c.532-7737T>C		intron	N/A	ENSP00000295930.3
	RSRC1	ENST00000312179.10	TSL:1	c.358-7737T>C		intron	N/A	ENSP00000308671.6

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62790 AN: 151954 Hom.: 13432 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.413 AC: 62830 AN: 152070 Hom.: 13440 Cov.: 33 AF XY: 0.417 AC XY: 31034 AN XY: 74346

African (AFR) AF: 0.338 AC: 14034 AN: 41474

American (AMR) AF: 0.432 AC: 6599 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1656 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3257 AN: 5174

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4822

European-Finnish (FIN) AF: 0.530 AC: 5604 AN: 10578

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.420 AC: 28574 AN: 67960

Other (OTH) AF: 0.443 AC: 937 AN: 2114

Alfa AF: 0.331 Hom.: 1352

Bravo AF: 0.407

Asia WGS AF: 0.419 AC: 1451 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		1.2
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: rs827135; hg19: chr3-158064909;