15-89731536-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020212.2(WDR93):c.1304T>G(p.Val435Gly) 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. 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: 1.16

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40782332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR93	NM_020212.2	c.1304T>G	p.Val435Gly	missense_variant	12/17	ENST00000268130.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR93	ENST00000268130.12	c.1304T>G	p.Val435Gly	missense_variant	12/17	1	NM_020212.2	P2
WDR93	ENST00000560294.5	c.1304T>G	p.Val435Gly	missense_variant	12/17	2		A2
WDR93	ENST00000444934.3	n.810T>G		non_coding_transcript_exon_variant	6/11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 31, 2023

The c.1304T>G (p.V435G) alteration is located in exon 12 (coding exon 11) of the WDR93 gene. This alteration results from a T to G substitution at nucleotide position 1304, causing the valine (V) at amino acid position 435 to be replaced by a glycine (G). 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	0.31
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.016	D;T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.92	P;P
Vest4		0.54
MutPred		0.39		Loss of stability (P = 0.0027);Loss of stability (P = 0.0027);
MVP		0.33
MPC		0.43
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.36
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1388682181; hg19: chr15-90274767;