Variant 1-108983284-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001142551.2(WDR47):c.2093C>T(p.Thr698Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,603,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

WDR47
NM_001142551.2 missense, splice_region

Scores

Splicing: ADA: 0.9982

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

WDR47 (HGNC:29141): (WD repeat domain 47) Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

WDR47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR47	NM_001142551.2 linkuse as main transcript	c.2093C>T	p.Thr698Ile	missense_variant, splice_region_variant	11/15	ENST00000369962.8	NP_001136023.1	O94967-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR47	ENST00000369962.8 linkuse as main transcript	c.2093C>T	p.Thr698Ile	missense_variant, splice_region_variant	11/15	1	NM_001142551.2	ENSP00000358979.3	O94967-1
WDR47	ENST00000400794.7 linkuse as main transcript	c.2117C>T	p.Thr706Ile	missense_variant, splice_region_variant	11/15	1		ENSP00000383599.3	O94967-4
WDR47	ENST00000369965.8 linkuse as main transcript	c.2096C>T	p.Thr699Ile	missense_variant, splice_region_variant	11/15	1		ENSP00000358982.4	O94967-3
WDR47	ENST00000361054.7 linkuse as main transcript	c.2009C>T	p.Thr670Ile	missense_variant, splice_region_variant	10/14	5		ENSP00000354339.3	O94967-2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000370

AC:

AN:

243424

Hom.:

AF XY:

0.0000379

AC XY:

AN XY:

132028

show subpopulations

Gnomad AFR exome

AF:

0.000576

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1451400

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

722160

show subpopulations

Gnomad4 AFR exome

AF:

0.000881

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:

9.03e-7

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.000164

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000602

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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 05, 2024

The c.2117C>T (p.T706I) alteration is located in exon 11 (coding exon 10) of the WDR47 gene. This alteration results from a C to T substitution at nucleotide position 2117, causing the threonine (T) at amino acid position 706 to be replaced by an isoleucine (I). 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

0.54

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

.;T;.;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D;T

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.55

.;N;.;.;.

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.6

N;N;N;N;N

REVEL

Uncertain

0.56

Sift

Benign

0.20

T;T;T;T;T

Sift4G

Benign

0.095

T;T;T;T;T

Polyphen

0.93, 0.93

.;P;P;P;.

Vest4

0.56

MVP

0.20

MPC

1.9

ClinPred

0.18

GERP RS

5.5

Varity_R

0.20

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.26

Position offset: -13

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