3-158122277-G-C

Variant names:

• chr3-158122277-G-C
• rs756866968
• NM_001271838.2:c.173G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001271838.2(RSRC1):​c.173G>C​(p.Arg58Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RSRC1 NM_001271838.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.16

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41149312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.173G>C	p.Arg58Pro	missense_variant	Exon 2 of 10	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.173G>C	p.Arg58Pro	missense_variant	Exon 2 of 10	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1430272 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 711484

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;T;T;T;T;.;.;T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	.;T;T;.;T;.;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.41	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.6	L;.;L;L;.;L;L;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.4	N;D;.;N;D;D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.032	D;T;.;D;D;T;T;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D;D;D;D;D
Polyphen		0.99	D;.;D;D;.;D;D;.;.
Vest4		0.55
MutPred		0.25		Gain of glycosylation at S61 (P = 0.0023);Gain of glycosylation at S61 (P = 0.0023);Gain of glycosylation at S61 (P = 0.0023);Gain of glycosylation at S61 (P = 0.0023);Gain of glycosylation at S61 (P = 0.0023);Gain of glycosylation at S61 (P = 0.0023);Gain of glycosylation at S61 (P = 0.0023);Gain of glycosylation at S61 (P = 0.0023);Gain of glycosylation at S61 (P = 0.0023);
MVP		0.90
MPC		0.11
ClinPred		0.87	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs756866968; hg19: chr3-157840066;