chr17-6080965-C-T

Variant names:

• chr17-6080965-C-T
• rs769471892
• NM_015253.2:c.307C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015253.2(WSCD1):​c.307C>T​(p.Arg103Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000707 in 1,554,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R103Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: WSCD1 NM_015253.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0820
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06476268).

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.307C>T	p.Arg103Trp	missense	Exon 2 of 9	NP_056068.1	Q658N2
	WSCD1	NM_001388405.1		c.307C>T	p.Arg103Trp	missense	Exon 2 of 9	NP_001375334.1	Q658N2
	WSCD1	NM_001388406.1		c.307C>T	p.Arg103Trp	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.307C>T	p.Arg103Trp	missense	Exon 2 of 9	ENSP00000323087.5	Q658N2
	WSCD1	ENST00000573634.5	TSL:1	c.80-7025C>T		intron	N/A	ENSP00000460396.1	I3L3E6
	WSCD1	ENST00000920366.1		c.307C>T	p.Arg103Trp	missense	Exon 3 of 11	ENSP00000590425.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000397 AC: 6 AN: 151230 AF XY: 0.0000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000239

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000570 AC: 8 AN: 1402650 Hom.: 0 Cov.: 31 AF XY: 0.00000433 AC XY: 3 AN XY: 693074

African (AFR) AF: 0.00 AC: 0 AN: 32454

American (AMR) AF: 0.000137 AC: 5 AN: 36532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25230

East Asian (EAS) AF: 0.00 AC: 0 AN: 37128

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1085456

Other (OTH) AF: 0.00 AC: 0 AN: 58414

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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: 0.0000147 AC: 1 AN: 68038

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000273 AC: 3

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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.082
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.28
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.023	D
Polyphen		0.96	D
Vest4		0.40
MutPred		0.38		Loss of helix (P = 0.0068)
MVP		0.52
MPC		0.40
ClinPred		0.19	T
GERP RS		3.5
Varity_R		0.13
gMVP		0.64
Mutation Taster		=94/6	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: rs769471892; hg19: chr17-5984285;