NM_020212.2:c.760T>G

Variant names:

• chr15-89716914-T-G
• rs7163367
• NM_020212.2:c.760T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020212.2(WDR93):​c.760T>G​(p.Ser254Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR93 NM_020212.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 29 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05129206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR93	NM_020212.2	c.760T>G	p.Ser254Ala	missense_variant	Exon 7 of 17	ENST00000268130.12	NP_064597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR93	ENST00000268130.12	c.760T>G	p.Ser254Ala	missense_variant	Exon 7 of 17	1	NM_020212.2	ENSP00000268130.7
WDR93	ENST00000560294.5	c.760T>G	p.Ser254Ala	missense_variant	Exon 7 of 17	2		ENSP00000453971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1410002 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 700734

African (AFR) AF: 0.00 AC: 0 AN: 30742

American (AMR) AF: 0.00 AC: 0 AN: 38636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25388

East Asian (EAS) AF: 0.00 AC: 0 AN: 37278

South Asian (SAS) AF: 0.00 AC: 0 AN: 76674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084198

Other (OTH) AF: 0.00 AC: 0 AN: 58356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.88
DANN	Benign	0.59
DEOGEN2	Benign	0.0026	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.089	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		-0.44
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.013
Sift	Benign	0.064	T;D
Sift4G	Benign	0.073	T;T
Polyphen		0.0020	B;B
Vest4		0.028
MutPred		0.14		Loss of disorder (P = 0.0485);Loss of disorder (P = 0.0485);
MVP		0.030
MPC		0.060
ClinPred		0.043	T
GERP RS		-2.3
Varity_R		0.048
gMVP		0.14

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: rs7163367; hg19: chr15-90260145;