Variant 2-223945203-T-A 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_020830.5(WDFY1):c.82A>T(p.Thr28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

WDFY1
NM_020830.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

Variant links:

Genes affected

WDFY1 (HGNC:20451): (WD repeat and FYVE domain containing 1) The protein encoded by this gene is a phosphatidylinositol 3-phosphate binding protein, which contains a FYVE zinc finger domain and multiple WD-40 repeat domains. When exogenously expressed, it localizes to early endosomes. Mutagenesis analysis demonstrates that this endosomal localization is mediated by the FYVE domain. [provided by RefSeq, Jan 2015]

WDFY1 links:

LOC124907989 (HGNC:):

LOC124907989 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=0.22231346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDFY1	NM_020830.5 linkuse as main transcript	c.82A>T	p.Thr28Ser	missense_variant	1/12	ENST00000233055.9
LOC124907989	XR_007088100.1 linkuse as main transcript	n.1184+796T>A		intron_variant, non_coding_transcript_variant
LOC124907989	XR_007088101.1 linkuse as main transcript	n.77+648T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WDFY1	ENST00000233055.9 linkuse as main transcript	c.82A>T	p.Thr28Ser	missense_variant	1/12	1	NM_020830.5	P1
WDFY1	ENST00000429915.1 linkuse as main transcript	c.82A>T	p.Thr28Ser	missense_variant	1/6	3
WDFY1	ENST00000483061.1 linkuse as main transcript	n.133A>T		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000888

AC:

AN:

225144

Hom.:

AF XY:

0.00

AC XY:

AN XY:

124394

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000125

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

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

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

May 03, 2023

The c.82A>T (p.T28S) alteration is located in exon 1 (coding exon 1) of the WDFY1 gene. This alteration results from a A to T substitution at nucleotide position 82, causing the threonine (T) at amino acid position 28 to be replaced by a serine (S). 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

0.074

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.67

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.36

N;N

REVEL

Benign

0.10

Sift

Benign

0.063

T;T

Sift4G

Benign

0.27

T;.

Polyphen

0.0

B;.

Vest4

0.071

MutPred

0.66

Gain of disorder (P = 0.0391);Gain of disorder (P = 0.0391);

MVP

0.29

MPC

0.35

ClinPred

0.39

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.064

gMVP

0.055

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