17-6080699-G-A

Variant names:

• chr17-6080699-G-A
• rs148296936
• NM_015253.2:c.41G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_015253.2(WSCD1):​c.41G>A​(p.Arg14Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000159 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: WSCD1 NM_015253.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.61
• Publications: 4 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36878377).

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.41G>A	p.Arg14Gln	missense	Exon 2 of 9	NP_056068.1	Q658N2
	WSCD1	NM_001388405.1		c.41G>A	p.Arg14Gln	missense	Exon 2 of 9	NP_001375334.1	Q658N2
	WSCD1	NM_001388406.1		c.41G>A	p.Arg14Gln	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.41G>A	p.Arg14Gln	missense	Exon 2 of 9	ENSP00000323087.5	Q658N2
	ENSG00000285471	ENST00000573619.1	TSL:2	c.41G>A	p.Arg14Gln	missense	Exon 5 of 5	ENSP00000461865.1	I3NI40
	WSCD1	ENST00000573634.5	TSL:1	c.80-7291G>A		intron	N/A	ENSP00000460396.1	I3L3E6

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000280 AC: 70 AN: 250186 AF XY: 0.000273

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000157 AC: 229 AN: 1461272 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 117 AN XY: 726962

African (AFR) AF: 0.0000598 AC: 2 AN: 33454

American (AMR) AF: 0.00112 AC: 50 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000138 AC: 153 AN: 1111900

Other (OTH) AF: 0.000199 AC: 12 AN: 60376

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74490

African (AFR) AF: 0.000144 AC: 6 AN: 41582

American (AMR) AF: 0.000719 AC: 11 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000287 Hom.: 1

Bravo AF: 0.000264

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000243 AC: 2

ExAC AF: 0.000207 AC: 25

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.063	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.62	D
MutationAssessor	Benign	1.8	L
PhyloP100		6.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.2	N
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.43
MVP		0.85
MPC		0.48
ClinPred		0.21	T
GERP RS		4.8
Varity_R		0.31
gMVP		0.71
Mutation Taster		=75/25	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: rs148296936; hg19: chr17-5984019; COSMIC: COSV100496568; COSMIC: COSV100496568;