17-6080815-C-T

Variant names:

• chr17-6080815-C-T
• rs546894775
• NM_015253.2:c.157C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015253.2(WSCD1):​c.157C>T​(p.Gln53*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000686 in 1,456,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WSCD1 NM_015253.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.157C>T	p.Gln53*	stop_gained	Exon 2 of 9	NP_056068.1	Q658N2
	WSCD1	NM_001388405.1		c.157C>T	p.Gln53*	stop_gained	Exon 2 of 9	NP_001375334.1	Q658N2
	WSCD1	NM_001388406.1		c.157C>T	p.Gln53*	stop_gained	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.157C>T	p.Gln53*	stop_gained	Exon 2 of 9	ENSP00000323087.5	Q658N2
	WSCD1	ENST00000573634.5	TSL:1	c.80-7175C>T		intron	N/A	ENSP00000460396.1	I3L3E6
	WSCD1	ENST00000920366.1		c.157C>T	p.Gln53*	stop_gained	Exon 3 of 11	ENSP00000590425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 234368 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 6.86e-7 AC: 1 AN: 1456876 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724564

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.00 AC: 0 AN: 85790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110562

Other (OTH) AF: 0.00 AC: 0 AN: 60142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		4.1
Vest4		0.22
GERP RS		4.5

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: rs546894775; hg19: chr17-5984135;