chr17-6081014-A-G

Position:

• chr17-6081014-A-G

Variant summary

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

The NM_015253.2(WSCD1):​c.356A>G​(p.His119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,392,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WSCD1 NM_015253.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.690

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=0.07168892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WSCD1	NM_015253.2	c.356A>G	p.His119Arg	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.356A>G	p.His119Arg	missense_variant	2/9	1	NM_015253.2	ENSP00000323087	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1392032 Hom.: 0 Cov.: 31 AF XY: 0.00000291 AC XY: 2 AN XY: 686696

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: 0.00000185

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

Sep 16, 2021

The c.356A>G (p.H119R) alteration is located in exon 2 (coding exon 1) of the WSCD1 gene. This alteration results from a A to G substitution at nucleotide position 356, causing the histidine (H) at amino acid position 119 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	0.066
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
DANN	Benign	0.53
DEOGEN2	Benign	0.0034	T;T;T;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.63	.;T;.;.;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.072	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.17	N;.;N;N;N
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.67	.;.;N;.;N
REVEL	Benign	0.19
Sift	Benign	0.71	.;.;T;.;T
Sift4G	Benign	0.72	T;T;T;T;T
Polyphen		0.0	B;.;B;B;B
Vest4		0.16
MutPred		0.34		Gain of MoRF binding (P = 0.0316);Gain of MoRF binding (P = 0.0316);Gain of MoRF binding (P = 0.0316);Gain of MoRF binding (P = 0.0316);Gain of MoRF binding (P = 0.0316);
MVP		0.18
MPC		0.30
ClinPred		0.040	T
GERP RS		1.2
Varity_R		0.069
gMVP		0.44

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: chr17-5984334;