Variant 14-54955676-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007086.4(WDHD1):c.2935T>A(p.Phe979Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000506 in 1,581,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

WDHD1
NM_007086.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82

Variant links:

Genes affected

WDHD1 (HGNC:23170): (WD repeat and HMG-box DNA binding protein 1) The protein encoded by this gene contains multiple N-terminal WD40 domains and a C-terminal high mobility group (HMG) box. WD40 domains are found in a variety of eukaryotic proteins and may function as adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

WDHD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37771237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDHD1	NM_007086.4 link	c.2935T>A	p.Phe979Ile	missense_variant	24/26	ENST00000360586.8	NP_009017.1	O75717-1
WDHD1	NM_001008396.3 link	c.2566T>A	p.Phe856Ile	missense_variant	23/25		NP_001008397.1	O75717-2
WDHD1	XM_006720012.2 link	c.2929T>A	p.Phe977Ile	missense_variant	24/26		XP_006720075.1
WDHD1	XM_011536373.3 link	c.1846T>A	p.Phe616Ile	missense_variant	15/17		XP_011534675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDHD1	ENST00000360586.8 link	c.2935T>A	p.Phe979Ile	missense_variant	24/26	1	NM_007086.4	ENSP00000353793.3	O75717-1
WDHD1	ENST00000420358.2 link	c.2566T>A	p.Phe856Ile	missense_variant	23/25	5		ENSP00000399349.2	O75717-2
WDHD1	ENST00000567693.1 link	n.*1385T>A		non_coding_transcript_exon_variant	12/14	2		ENSP00000456806.1	H3BSQ1
WDHD1	ENST00000567693.1 link	n.*1385T>A		3_prime_UTR_variant	12/14	2		ENSP00000456806.1	H3BSQ1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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

GnomAD4 exome

AF:

0.00000420

AC:

AN:

1428898

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

710822

show subpopulations

Gnomad4 AFR exome

AF:

0.000192

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

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

Jan 26, 2022

The c.2935T>A (p.F979I) alteration is located in exon 24 (coding exon 23) of the WDHD1 gene. This alteration results from a T to A substitution at nucleotide position 2935, causing the phenylalanine (F) at amino acid position 979 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

Benign

0.20

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.057

T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.16

Sift

Benign

0.051

T;D

Sift4G

Benign

0.12

T;T

Polyphen

0.88

P;.

Vest4

0.51

MVP

0.80

MPC

0.30

ClinPred

0.65

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.11

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