3-158122232-A-G

Position:

• chr3-158122232-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001271838.2(RSRC1):​c.128A>G​(p.Lys43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 0.0000014 (0 hom.)
• Consequence: RSRC1 NM_001271838.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076143146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.128A>G	p.Lys43Arg	missense_variant	2/10	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.128A>G	p.Lys43Arg	missense_variant	2/10	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453608 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 723152

Gnomad4 AFR exome AF: 0.0000304

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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

Oct 08, 2024

The c.128A>G (p.K43R) alteration is located in exon 2 (coding exon 1) of the RSRC1 gene. This alteration results from a A to G substitution at nucleotide position 128, causing the lysine (K) at amino acid position 43 to be replaced by an arginine (R). 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	Benign	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.014	T;T;T;T;T;.;.;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.64	.;T;T;.;T;.;T;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.076	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;N;N;.;N;N;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.10	N;N;.;N;N;N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.55	T;T;.;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;B;.;B;B;.;.
Vest4		0.16
MutPred		0.34		Gain of glycosylation at S46 (P = 2e-04);Gain of glycosylation at S46 (P = 2e-04);Gain of glycosylation at S46 (P = 2e-04);Gain of glycosylation at S46 (P = 2e-04);Gain of glycosylation at S46 (P = 2e-04);Gain of glycosylation at S46 (P = 2e-04);Gain of glycosylation at S46 (P = 2e-04);Gain of glycosylation at S46 (P = 2e-04);Gain of glycosylation at S46 (P = 2e-04);
MVP		0.74
MPC		0.062
ClinPred		0.43	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.15

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: rs899422612; hg19: chr3-157840021;