chr15-89716914-T-A

Position:

• chr15-89716914-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020212.2(WDR93):​c.760T>A​(p.Ser254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,555,692 control chromosomes in the GnomAD database, including 145,383 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (14008 hom., cov: 32)
  • Exomes 𝑓: 0.43 (131375 hom.)
• Consequence: WDR93 NM_020212.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1756467E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR93	NM_020212.2	c.760T>A	p.Ser254Thr	missense_variant	7/17	ENST00000268130.12	NP_064597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR93	ENST00000268130.12	c.760T>A	p.Ser254Thr	missense_variant	7/17	1	NM_020212.2	ENSP00000268130.7
WDR93	ENST00000560294.5	c.760T>A	p.Ser254Thr	missense_variant	7/17	2		ENSP00000453971.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63953 AN: 151866 Hom.: 13991 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.398

GnomAD3 exomes AF: 0.377 AC: 83817 AN: 222306 Hom.: 17116 AF XY: 0.384 AC XY: 46428 AN XY: 120874

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.443

Gnomad EAS exome AF: 0.194

Gnomad SAS exome AF: 0.405

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.427 AC: 598829 AN: 1403710 Hom.: 131375 Cov.: 29 AF XY: 0.426 AC XY: 297563 AN XY: 697730

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.421 AC: 64023 AN: 151982 Hom.: 14008 Cov.: 32 AF XY: 0.411 AC XY: 30569 AN XY: 74298

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.397

Alfa AF: 0.430 Hom.: 11198

Bravo AF: 0.425

TwinsUK AF: 0.465 AC: 1726

ALSPAC AF: 0.447 AC: 1721

ESP6500AA AF: 0.471 AC: 2074

ESP6500EA AF: 0.441 AC: 3788

ExAC AF: 0.391 AC: 47502

Asia WGS AF: 0.341 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.090
DANN	Benign	0.36
DEOGEN2	Benign	0.0016	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00029	N
LIST_S2	Benign	0.13	T;T
MetaRNN	Benign	0.00012	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.95	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.020
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.014
MPC		0.065
ClinPred		0.0027	T
GERP RS		-2.3
Varity_R		0.043
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs7163367; hg19: chr15-90260145; COSMIC: COSV51534060; COSMIC: COSV51534060;