chr17-6080798-G-C

Position:

• chr17-6080798-G-C

Variant summary

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

The NM_015253.2(WSCD1):​c.140G>C​(p.Arg47Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WSCD1 NM_015253.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

Genes affected

WSCD1 (HGNC:29060): (WSC domain containing 1) Predicted to enable sulfotransferase activity. Predicted to be located in membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2698014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WSCD1	NM_015253.2	c.140G>C	p.Arg47Pro	missense_variant	2/9	ENST00000317744.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WSCD1	ENST00000317744.10	c.140G>C	p.Arg47Pro	missense_variant	2/9	1	NM_015253.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.140G>C (p.R47P) alteration is located in exon 2 (coding exon 1) of the WSCD1 gene. This alteration results from a G to C substitution at nucleotide position 140, causing the arginine (R) at amino acid position 47 to be replaced by a proline (P). 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	0.10
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0084	T;T;T;T;T;.
Eigen	Benign	0.089
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.78	.;T;.;.;T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;M;M;M;.
MutationTaster	Benign	0.90	D;N;N;N;N
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.87	.;.;N;.;N;.
REVEL	Benign	0.12
Sift	Benign	0.34	.;.;T;.;T;.
Sift4G	Benign	0.30	T;T;T;T;T;T
Polyphen		0.99	D;.;D;D;D;.
Vest4		0.42
MutPred		0.26		Gain of glycosylation at R47 (P = 0.0056);Gain of glycosylation at R47 (P = 0.0056);Gain of glycosylation at R47 (P = 0.0056);Gain of glycosylation at R47 (P = 0.0056);Gain of glycosylation at R47 (P = 0.0056);Gain of glycosylation at R47 (P = 0.0056);
MVP		0.21
MPC		0.36
ClinPred		0.72	D
GERP RS		3.1
Varity_R		0.17
gMVP		0.52

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: chr17-5984118;