rs292592

chr7-135204389-G-Achr7-135204389-G-T

Variant summary

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

The NM_014149.4(WDR91):c.770C>T(p.Pro257Leu) variant causes a missense change. The variant allele was found at a frequency of 0.721 in 1,613,788 control chromosomes in the GnomAD database, including 422,427 homozygotes. In-silico tool predicts 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.68 (35855 hom., cov: 32)
  • Exomes 𝑓: 0.73 (386572 hom.)
• Consequence: WDR91 NM_014149.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50

Genes affected

WDR91 (HGNC:24997): (WD repeat domain 91) Enables phosphatidylinositol 3-kinase regulator activity. Involved in early endosome to late endosome transport; regulation of cellular protein catabolic process; and regulation of phosphatidylinositol 3-kinase activity. Located in cytosol; early endosome membrane; and late endosome membrane. Is extrinsic component of endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1990732E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR91	NM_014149.4	c.770C>T	p.Pro257Leu	missense_variant	6/15	ENST00000354475.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR91	ENST00000354475.5	c.770C>T	p.Pro257Leu	missense_variant	6/15	1	NM_014149.4	P1
	ENST00000628498.1	n.317+2842G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103323 AN: 151950 Hom.: 35836 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.728

GnomAD3 exomes AF: 0.720 AC: 180594 AN: 250966 Hom.: 65712 AF XY: 0.722 AC XY: 97931 AN XY: 135672

Gnomad AFR exome AF: 0.527

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.582

Gnomad SAS exome AF: 0.744

Gnomad FIN exome AF: 0.724

Gnomad NFE exome AF: 0.730

Gnomad OTH exome AF: 0.729

GnomAD4 exome AF: 0.726 AC: 1060762 AN: 1461720 Hom.: 386572 Cov.: 58 AF XY: 0.727 AC XY: 528299 AN XY: 727164

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.731

Gnomad4 EAS exome AF: 0.598

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.728

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.717

GnomAD4 genome AF: 0.680 AC: 103389 AN: 152068 Hom.: 35855 Cov.: 32 AF XY: 0.681 AC XY: 50589 AN XY: 74328

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.730

Alfa AF: 0.722 Hom.: 94980

Bravo AF: 0.678

TwinsUK AF: 0.744 AC: 2760

ALSPAC AF: 0.727 AC: 2803

ESP6500AA AF: 0.550 AC: 2423

ESP6500EA AF: 0.724 AC: 6223

ExAC AF: 0.713 AC: 86547

Asia WGS AF: 0.690 AC: 2397 AN: 3478

EpiCase AF: 0.729

EpiControl AF: 0.732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.70	T;T
MetaRNN	Benign	0.0000012	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.0000060	P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Benign	0.15
Sift	Benign	0.23	T;T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.90	.;P
Vest4		0.12
MPC		0.57
ClinPred		0.014	T
GERP RS		5.4
Varity_R		0.14
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs292592; hg19: chr7-134889141; COSMIC: COSV60371347; COSMIC: COSV60371347;