15-89701765-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020212.2(WDR93):c.19A>T(p.Ser7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR93 NM_020212.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02

Genes affected

WDR93 (HGNC:26924): (WD repeat domain 93) Predicted to enable oxidoreductase activity, acting on NAD(P)H. Predicted to be involved in electron transport chain. Predicted to be part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1402582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR93	NM_020212.2	c.19A>T	p.Ser7Cys	missense_variant	2/17	ENST00000268130.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR93	ENST00000268130.12	c.19A>T	p.Ser7Cys	missense_variant	2/17	1	NM_020212.2	P2
WDR93	ENST00000558000.1	c.19A>T	p.Ser7Cys	missense_variant	2/3	1		A2
WDR93	ENST00000560294.5	c.19A>T	p.Ser7Cys	missense_variant	2/17	2		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2024

The c.19A>T (p.S7C) alteration is located in exon 2 (coding exon 1) of the WDR93 gene. This alteration results from a A to T substitution at nucleotide position 19, causing the serine (S) at amino acid position 7 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	15
Dann	Uncertain	0.97
DEOGEN2	Benign	0.0061	T;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N;N;D
REVEL	Benign	0.10
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.97	D;P;D
Vest4		0.28
MutPred		0.12		Loss of phosphorylation at S7 (P = 0.0468);Loss of phosphorylation at S7 (P = 0.0468);Loss of phosphorylation at S7 (P = 0.0468);
MVP		0.092
MPC		0.36
ClinPred		0.57	D
GERP RS		3.1
Varity_R		0.096
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-90244996;