NM_014653.4:c.458A>T

Variant names:

• chr12-108206364-A-T
• rs527943874
• NM_014653.4:c.458A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014653.4(WSCD2):​c.458A>T​(p.Lys153Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. K153R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WSCD2 NM_014653.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88
• Publications: 0 publications found

Genes affected

WSCD2 (HGNC:29117): (WSC domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307044 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.788

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014653.4. 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
	WSCD2	NM_014653.4	MANE Select	c.458A>T	p.Lys153Met	missense	Exon 3 of 9	NP_055468.2
	WSCD2	NM_001304447.2		c.458A>T	p.Lys153Met	missense	Exon 4 of 10	NP_001291376.1	Q2TBF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WSCD2	ENST00000547525.6	TSL:1 MANE Select	c.458A>T	p.Lys153Met	missense	Exon 3 of 9	ENSP00000448047.1	Q2TBF2-1
	WSCD2	ENST00000332082.8	TSL:1	c.458A>T	p.Lys153Met	missense	Exon 4 of 10	ENSP00000331933.4	Q2TBF2-1
	WSCD2	ENST00000551638.5	TSL:4	c.-2A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000446744.1	F8W030

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.011	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		6.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.55		Gain of catalytic residue at K152 (P = 2e-04)
MVP		0.36
MPC		1.4
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.51
gMVP		0.82
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs527943874; hg19: chr12-108600141;