chr17-6088064-A-G

Position:

• chr17-6088064-A-G

Variant summary

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

The NM_015253.2(WSCD1):​c.502A>G​(p.Lys168Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WSCD1 NM_015253.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.12

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WSCD1	NM_015253.2	c.502A>G	p.Lys168Glu	missense_variant	3/9	ENST00000317744.10	NP_056068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WSCD1	ENST00000317744.10	c.502A>G	p.Lys168Glu	missense_variant	3/9	1	NM_015253.2	ENSP00000323087	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

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: 0.00000180

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

Jun 21, 2021

The c.502A>G (p.K168E) alteration is located in exon 3 (coding exon 2) of the WSCD1 gene. This alteration results from a A to G substitution at nucleotide position 502, causing the lysine (K) at amino acid position 168 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	0.88
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T;T;T;T;T;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	.;D;D;.;.;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.9	L;.;.;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.7	.;.;.;D;.;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	.;.;.;D;.;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D
Polyphen		1.0	D;.;.;D;D;D
Vest4		0.62
MutPred		0.53		Loss of ubiquitination at K168 (P = 0.0134);.;Loss of ubiquitination at K168 (P = 0.0134);Loss of ubiquitination at K168 (P = 0.0134);Loss of ubiquitination at K168 (P = 0.0134);Loss of ubiquitination at K168 (P = 0.0134);
MVP		0.44
MPC		1.1
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.74
gMVP		0.84

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: chr17-5991384;