Variant chrX-70239898-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The ENST00000374521.4(AWAT1):c.796G>A(p.Gly266Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,208,461 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 193 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., 7 hem., cov: 22)

Exomes 𝑓: 0.00048 ( 0 hom. 186 hem. )

Consequence

AWAT1
ENST00000374521.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.65

Variant links:

Genes affected

AWAT1 (HGNC:23252): (acyl-CoA wax alcohol acyltransferase 1) The protein encoded by this gene belongs to the diacylglycerol acyltransferase family. It esterifies long chain (wax) alcohols with acyl-CoA-derived fatty acids to produce wax esters. Wax esters are enriched in sebum, suggesting that this enzyme plays a central role in lipid metabolism in skin. Consistent with this observation, this protein is predominantly expressed in the sebaceous gland of the skin. [provided by RefSeq, Sep 2009]

AWAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant X-70239898-G-A is Benign according to our data. Variant chrX-70239898-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2349592.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AWAT1	NM_001013579.3 linkuse as main transcript	c.796G>A	p.Gly266Arg	missense_variant	6/7	ENST00000374521.4	NP_001013597.1	Q58HT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AWAT1	ENST00000374521.4 linkuse as main transcript	c.796G>A	p.Gly266Arg	missense_variant	6/7	1	NM_001013579.3	ENSP00000363645.3		Q58HT5

Frequencies

GnomAD3 genomes

AF:

0.000306

AC:

AN:

111018

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

AN XY:

33228

show subpopulations

Gnomad AFR

AF:

0.0000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000961

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000672

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000509

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000383

AC:

AN:

182939

Hom.:

AF XY:

0.000444

AC XY:

AN XY:

67497

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.000189

Gnomad NFE exome

AF:

0.000735

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000484

AC:

531

AN:

1097390

Hom.:

Cov.:

AF XY:

0.000513

AC XY:

186

AN XY:

362806

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.000346

Gnomad4 NFE exome

AF:

0.000571

Gnomad4 OTH exome

AF:

0.000608

GnomAD4 genome

AF:

0.000306

AC:

AN:

111071

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

33291

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.0000959

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000672

Gnomad4 NFE

AF:

0.000509

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000674

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000534

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.796G>A (p.G266R) alteration is located in exon 6 (coding exon 6) of the AWAT1 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the glycine (G) at amino acid position 266 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

AWAT1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.74

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.50

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.63

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.33

MutPred

0.95

Loss of catalytic residue at L267 (P = 0.1044);

MVP

0.73

MPC

0.75

ClinPred

0.48

GERP RS

5.4

Varity_R

0.81

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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