17-6081001-C-A

Position:

• chr17-6081001-C-A

Variant summary

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

The NM_015253.2(WSCD1):​c.343C>A​(p.Arg115Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 7.2e-7 (0 hom.)
• Consequence: WSCD1 NM_015253.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20115638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WSCD1	NM_015253.2	c.343C>A	p.Arg115Ser	missense_variant	2/9	ENST00000317744.10	NP_056068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WSCD1	ENST00000317744.10	c.343C>A	p.Arg115Ser	missense_variant	2/9	1	NM_015253.2	ENSP00000323087.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393128 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 687374

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

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

Jul 26, 2024

The c.343C>A (p.R115S) alteration is located in exon 2 (coding exon 1) of the WSCD1 gene. This alteration results from a C to A substitution at nucleotide position 343, causing the arginine (R) at amino acid position 115 to be replaced by a serine (S). 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	0.27
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;T;T;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.82	.;T;.;.;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M;.;M;M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.4	.;.;N;.;N
REVEL	Benign	0.27
Sift	Benign	0.082	.;.;T;.;T
Sift4G	Benign	0.16	T;D;T;T;T
Polyphen		0.36	B;.;B;B;B
Vest4		0.56
MutPred		0.41		Gain of phosphorylation at R115 (P = 0.0223);Gain of phosphorylation at R115 (P = 0.0223);Gain of phosphorylation at R115 (P = 0.0223);Gain of phosphorylation at R115 (P = 0.0223);Gain of phosphorylation at R115 (P = 0.0223);
MVP		0.28
MPC		0.34
ClinPred		0.49	T
GERP RS		3.7
Varity_R		0.19
gMVP		0.79

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: chr17-5984321;