Variant 10-28534015-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016628.5(WAC):c.59G>A(p.Gly20Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,260 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

WAC
NM_016628.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Variant links:

Genes affected

WAC (HGNC:17327): (WW domain containing adaptor with coiled-coil) The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

WAC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WAC	NM_016628.5 link	c.59G>A	p.Gly20Glu	missense_variant	2/14	ENST00000354911.9	NP_057712.2	Q9BTA9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WAC	ENST00000354911.9 link	c.59G>A	p.Gly20Glu	missense_variant	2/14	1	NM_016628.5	ENSP00000346986.4	Q9BTA9-1
WAC	ENST00000651885.1 link	c.59G>A	p.Gly20Glu	missense_variant	2/5			ENSP00000498678.1	A0A494C0S5
WAC	ENST00000428935 link	c.-77G>A		5_prime_UTR_variant	2/8	2		ENSP00000399706.3	A0A0A0MSR1
WAC	ENST00000651598 link	c.-95G>A		5_prime_UTR_variant	2/6			ENSP00000498480.1	A0A494C0C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000428

AC:

AN:

233584

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127564

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.59G>A (p.G20E) alteration is located in exon 1 (coding exon 1) of the WAC gene. This alteration results from a G to A substitution at nucleotide position 59, causing the glycine (G) at amino acid position 20 to be replaced by a glutamic acid (E). 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

0.28

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0097

.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.86

D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.19

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.017

D;.

Sift4G

Benign

0.41

T;T

Polyphen

1.0

D;D

Vest4

0.75

MutPred

0.20

Loss of MoRF binding (P = 0.0385);Loss of MoRF binding (P = 0.0385);

MVP

0.068

MPC

0.68

ClinPred

0.45

GERP RS

4.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.32

gMVP

0.10

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