Variant chr3-167505396-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366157.1(WDR49):c.2795T>C(p.Ile932Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,522,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

WDR49
NM_001366157.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.285

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059674203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDR49	NM_001366157.1 linkuse as main transcript	c.2795T>C	p.Ile932Thr	missense_variant	17/19	ENST00000682715.1
WDR49	NM_001348951.2 linkuse as main transcript	c.2762T>C	p.Ile921Thr	missense_variant	17/19
WDR49	NM_001348952.2 linkuse as main transcript	c.2762T>C	p.Ile921Thr	missense_variant	17/19
WDR49	NM_001366158.1 linkuse as main transcript	c.1739T>C	p.Ile580Thr	missense_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR49	ENST00000682715.1 linkuse as main transcript	c.2795T>C	p.Ile932Thr	missense_variant	17/19		NM_001366157.1	A2

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000418

AC:

AN:

186680

Hom.:

AF XY:

0.000436

AC XY:

AN XY:

103304

show subpopulations

Gnomad AFR exome

AF:

0.0000811

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000414

Gnomad NFE exome

AF:

0.000698

Gnomad OTH exome

AF:

0.000743

GnomAD4 exome

AF:

0.000428

AC:

586

AN:

1369752

Hom.:

Cov.:

AF XY:

0.000408

AC XY:

277

AN XY:

679132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000700

Gnomad4 AMR exome

AF:

0.000152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000287

Gnomad4 FIN exome

AF:

0.000509

Gnomad4 NFE exome

AF:

0.000491

Gnomad4 OTH exome

AF:

0.000445

GnomAD4 genome

AF:

0.000374

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000488

Hom.:

Bravo

AF:

0.000374

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000705

AC:

ExAC

AF:

0.000446

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

Dec 14, 2023

The c.1739T>C (p.I580T) alteration is located in exon 13 (coding exon 12) of the WDR49 gene. This alteration results from a T to C substitution at nucleotide position 1739, causing the isoleucine (I) at amino acid position 580 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

Benign

0.078

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.9

DANN

Benign

0.96

DEOGEN2

Benign

0.00021

T;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.40

T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.060

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.93

N;.;.

REVEL

Benign

0.063

Sift

Benign

0.62

T;.;.

Sift4G

Benign

0.55

T;.;.

Polyphen

0.0030

B;.;.

Vest4

0.22

MVP

0.51

MPC

0.033

ClinPred

1.0

GERP RS

0.73

Varity_R

0.024

gMVP

0.038

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

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