17-6080944-C-T

Variant names:

• chr17-6080944-C-T
• rs370966557
• NM_015253.2:c.286C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015253.2(WSCD1):​c.286C>T​(p.Arg96Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,566,870 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: WSCD1 NM_015253.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

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]

ENSG00000285471 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11031541).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015253.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WSCD1	NM_015253.2	MANE Select	c.286C>T	p.Arg96Trp	missense	Exon 2 of 9	NP_056068.1	Q658N2
	WSCD1	NM_001388405.1		c.286C>T	p.Arg96Trp	missense	Exon 2 of 9	NP_001375334.1	Q658N2
	WSCD1	NM_001388406.1		c.286C>T	p.Arg96Trp	missense	Exon 2 of 9	NP_001375335.1	Q658N2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WSCD1	ENST00000317744.10	TSL:1 MANE Select	c.286C>T	p.Arg96Trp	missense	Exon 2 of 9	ENSP00000323087.5	Q658N2
	WSCD1	ENST00000573634.5	TSL:1	c.80-7046C>T		intron	N/A	ENSP00000460396.1	I3L3E6
	WSCD1	ENST00000920366.1		c.286C>T	p.Arg96Trp	missense	Exon 3 of 11	ENSP00000590425.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000132 AC: 22 AN: 166038 AF XY: 0.000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000984

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000175 AC: 247 AN: 1414664 Hom.: 1 Cov.: 31 AF XY: 0.000179 AC XY: 125 AN XY: 700254

African (AFR) AF: 0.0000912 AC: 3 AN: 32896

American (AMR) AF: 0.00 AC: 0 AN: 38188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25338

East Asian (EAS) AF: 0.000448 AC: 17 AN: 37948

South Asian (SAS) AF: 0.0000246 AC: 2 AN: 81240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.000198 AC: 216 AN: 1092662

Other (OTH) AF: 0.000153 AC: 9 AN: 58898

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152206 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.000140

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000126 AC: 1

ExAC AF: 0.000107 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.30
MVP		0.75
MPC		0.27
ClinPred		0.17	T
GERP RS		2.3
Varity_R		0.096
gMVP		0.63
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs370966557; hg19: chr17-5984264;