7-135188542-A-G

Position:

• chr7-135188542-A-G

Variant summary

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

The NM_014149.4(WDR91):​c.1772T>C​(p.Met591Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR91 NM_014149.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.70

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]

WDR91 (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/exons	MANE	Protein	UniProt
WDR91	NM_014149.4	c.1772T>C	p.Met591Thr	missense_variant	13/15	ENST00000354475.5	NP_054868.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR91	ENST00000354475.5	c.1772T>C	p.Met591Thr	missense_variant	13/15	1	NM_014149.4	ENSP00000346466.4
WDR91	ENST00000423565.5	c.1667T>C	p.Met556Thr	missense_variant	13/15	5		ENSP00000392555.1

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

Nov 25, 2024

The c.1772T>C (p.M591T) alteration is located in exon 13 (coding exon 13) of the WDR91 gene. This alteration results from a T to C substitution at nucleotide position 1772, causing the methionine (M) at amino acid position 591 to be replaced by a threonine (T). 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	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	-0.075	.;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0050	D;T
Polyphen		0.93	.;P
Vest4		0.87
MutPred		0.52		.;Loss of stability (P = 0.0258);
MVP		0.36
MPC		0.54
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.64
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-134873294;