Variant 7-135188501-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014149.4(WDR91):c.1813G>A(p.Gly605Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

WDR91
NM_014149.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 link	c.1813G>A	p.Gly605Arg	missense_variant	13/15	ENST00000354475.5	NP_054868.3	A4D1P6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR91	ENST00000354475.5 link	c.1813G>A	p.Gly605Arg	missense_variant	13/15	1	NM_014149.4	ENSP00000346466.4		A4D1P6-1
WDR91	ENST00000423565.5 link	c.1708G>A	p.Gly570Arg	missense_variant	13/15	5		ENSP00000392555.1		C9J1X0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251374

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.1813G>A (p.G605R) alteration is located in exon 13 (coding exon 13) of the WDR91 gene. This alteration results from a G to A substitution at nucleotide position 1813, causing the glycine (G) at amino acid position 605 to be replaced by an arginine (R). 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

.;M

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.30

.;B

Vest4

0.84

MutPred

0.52

.;Loss of catalytic residue at E606 (P = 0.116);

MVP

0.49

MPC

0.81

ClinPred

0.98

GERP RS

5.8

Varity_R

0.48

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over