Variant 3-167505339-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366157.1(WDR49):c.2852C>A(p.Pro951His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,523,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

WDR49
NM_001366157.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.195

Variant links:

Genes affected

WDR49 (HGNC:26587): (WD repeat domain 49) This gene encodes a member of the WD repeat protein family with nine WD repeats. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

WDR49 links:

WDR49 (HGNC:):

WDR49 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09242073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WDR49	NM_001366157.1 linkuse as main transcript	c.2852C>A	p.Pro951His	missense_variant	17/19	ENST00000682715.1	NP_001353086.1
WDR49	NM_001348951.2 linkuse as main transcript	c.2819C>A	p.Pro940His	missense_variant	17/19		NP_001335880.1
WDR49	NM_001348952.2 linkuse as main transcript	c.2819C>A	p.Pro940His	missense_variant	17/19		NP_001335881.1
WDR49	NM_001366158.1 linkuse as main transcript	c.1796C>A	p.Pro599His	missense_variant	14/16		NP_001353087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR49	ENST00000682715.1 linkuse as main transcript	c.2852C>A	p.Pro951His	missense_variant	17/19		NM_001366157.1	ENSP00000507497.1		A0A804HJG6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000156

AC:

AN:

192206

Hom.:

AF XY:

0.00000946

AC XY:

AN XY:

105756

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1371586

Hom.:

Cov.:

AF XY:

0.0000118

AC XY:

AN XY:

679666

show subpopulations

Gnomad4 AFR exome

AF:

0.0000346

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000441

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000149

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152000

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000435

Hom.:

Bravo

AF:

0.00000756

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

Aug 11, 2024

The c.1796C>A (p.P599H) alteration is located in exon 13 (coding exon 12) of the WDR49 gene. This alteration results from a C to A substitution at nucleotide position 1796, causing the proline (P) at amino acid position 599 to be replaced by a histidine (H). 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

Benign

0.071

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.7

DANN

Benign

0.34

DEOGEN2

Benign

0.0048

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.1

N;.;.

REVEL

Benign

0.017

Sift

Benign

0.24

T;.;.

Sift4G

Benign

0.33

T;.;.

Polyphen

0.41

B;.;.

Vest4

0.16

MutPred

0.36

Gain of glycosylation at Y600 (P = 0.0349);.;.;

MVP

0.25

MPC

0.031

ClinPred

0.044

GERP RS

-2.4

Varity_R

0.055

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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