3-158123943-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001271838.2(RSRC1):c.272G>A(p.Gly91Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSRC1 NM_001271838.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSRC1	NM_001271838.2	c.272G>A	p.Gly91Glu	missense_variant	3/10	ENST00000611884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSRC1	ENST00000611884.5	c.272G>A	p.Gly91Glu	missense_variant	3/10	5	NM_001271838.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.272G>A (p.G91E) alteration is located in exon 3 (coding exon 2) of the RSRC1 gene. This alteration results from a G to A substitution at nucleotide position 272, causing the glycine (G) at amino acid position 91 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T;T;T;T;.;.;T;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.7	L;.;L;L;.;L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.1	D;D;.;D;D;D;D;D;D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;D;.;D;D;T;T;D;D
Sift4G	Uncertain	0.046	D;T;D;D;T;T;T;T;T
Polyphen		1.0	D;.;D;D;.;D;D;.;.
Vest4		0.60
MutPred		0.33		Gain of glycosylation at S93 (P = 0);Gain of glycosylation at S93 (P = 0);Gain of glycosylation at S93 (P = 0);Gain of glycosylation at S93 (P = 0);Gain of glycosylation at S93 (P = 0);Gain of glycosylation at S93 (P = 0);Gain of glycosylation at S93 (P = 0);Gain of glycosylation at S93 (P = 0);Gain of glycosylation at S93 (P = 0);
MVP		0.94
MPC		0.096
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.21

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-157841732; COSMIC: COSV99907369;