chr15-89701880-A-T

Position:

• chr15-89701880-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020212.2(WDR93):​c.134A>T​(p.Asp45Val) 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 pathogenic 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: 2.88

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]

WDR93 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR93	NM_020212.2	c.134A>T	p.Asp45Val	missense_variant	2/17	ENST00000268130.12	NP_064597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR93	ENST00000268130.12	c.134A>T	p.Asp45Val	missense_variant	2/17	1	NM_020212.2	ENSP00000268130.7
WDR93	ENST00000558000.1	c.134A>T	p.Asp45Val	missense_variant	2/3	1		ENSP00000453022.1
WDR93	ENST00000560294.5	c.134A>T	p.Asp45Val	missense_variant	2/17	2		ENSP00000453971.1

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

Jun 18, 2024

The c.134A>T (p.D45V) 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 134, causing the aspartic acid (D) at amino acid position 45 to be replaced by a valine (V). 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	0.16
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-7.1	D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.71
MutPred		0.42		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.59
MPC		0.48
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.62
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr15-90245111;