Variant 9-113331099-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_001012361.4(WDR31):c.134T>C(p.Ile45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,407,128 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

WDR31
NM_001012361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00200

Variant links:

Genes affected

WDR31 (HGNC:21421): (WD repeat domain 31) This gene encodes a member of the WD repeat protein family. 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. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

WDR31 links:

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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=0.05596155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR31	NM_001012361.4 linkuse as main transcript	c.134T>C	p.Ile45Thr	missense_variant	4/11	ENST00000374193.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR31	ENST00000374193.9 linkuse as main transcript	c.134T>C	p.Ile45Thr	missense_variant	4/11	1	NM_001012361.4	P4	Q8NA23-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000284

AC:

AN:

1407128

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698786

show subpopulations

Gnomad4 AFR exome

AF:

0.0000927

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.30e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

May 14, 2024

The c.134T>C (p.I45T) alteration is located in exon 4 (coding exon 2) of the WDR31 gene. This alteration results from a T to C substitution at nucleotide position 134, causing the isoleucine (I) at amino acid position 45 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

0.059

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.2

DANN

Benign

0.81

DEOGEN2

Benign

0.0024

.;T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.60

.;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.65

N;N;.

REVEL

Benign

0.065

Sift

Benign

0.18

T;T;.

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.12

MutPred

0.42

.;Gain of disorder (P = 0.0193);.;

MVP

0.50

MPC

0.14

ClinPred

0.064

GERP RS

0.36

Varity_R

0.050

gMVP

0.25

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