7-135204389-G-T

Variant names:

• chr7-135204389-G-T
• rs292592
• NM_014149.4:c.770C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014149.4(WDR91):​c.770C>A​(p.Pro257His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P257L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• 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]

ENSG00000231794 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR91	NM_014149.4	c.770C>A	p.Pro257His	missense_variant	Exon 6 of 15	ENST00000354475.5	NP_054868.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR91	ENST00000354475.5	c.770C>A	p.Pro257His	missense_variant	Exon 6 of 15	1	NM_014149.4	ENSP00000346466.4
WDR91	ENST00000423565.5	c.665C>A	p.Pro222His	missense_variant	Exon 6 of 15	5		ENSP00000392555.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.22
Sift	Benign	0.054	T;T
Sift4G	Uncertain	0.0020	D;T
Polyphen		1.0	.;D
Vest4		0.39
MutPred		0.36		.;Loss of loop (P = 0.0203);
MVP		0.64
MPC		0.92
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.14
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: rs292592; hg19: chr7-134889141;