Variant X-70240234-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000374521.4(AWAT1):c.931G>A(p.Asp311Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,209,835 control chromosomes in the GnomAD database, including 1 homozygotes. There are 38 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 1 hom. 35 hem. )

Consequence

AWAT1
ENST00000374521.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05693817).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AWAT1	NM_001013579.3 linkuse as main transcript	c.931G>A	p.Asp311Asn	missense_variant	7/7	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.931G>A	p.Asp311Asn	missense_variant	7/7	1	NM_001013579.3	ENSP00000363645.3		Q58HT5

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

111943

Hom.:

Cov.:

AF XY:

0.0000879

AC XY:

AN XY:

34113

show subpopulations

Gnomad AFR

AF:

0.0000649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000940

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000186

AC:

AN:

183076

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

67628

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000216

Gnomad SAS exome

AF:

0.000315

Gnomad FIN exome

AF:

0.000876

Gnomad NFE exome

AF:

0.0000980

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000107

AC:

118

AN:

1097892

Hom.:

Cov.:

AF XY:

0.0000963

AC XY:

AN XY:

363262

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.000369

Gnomad4 FIN exome

AF:

0.000691

Gnomad4 NFE exome

AF:

0.0000725

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.000107

AC:

AN:

111943

Hom.:

Cov.:

AF XY:

0.0000879

AC XY:

AN XY:

34113

show subpopulations

Gnomad4 AFR

AF:

0.0000649

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.0000940

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Oct 04, 2022

The c.931G>A (p.D311N) alteration is located in exon 7 (coding exon 7) of the AWAT1 gene. This alteration results from a G to A substitution at nucleotide position 931, causing the aspartic acid (D) at amino acid position 311 to be replaced by an asparagine (N). 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

0.095

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0014

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.96

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.2

REVEL

Benign

0.10

Sift

Benign

0.11

Sift4G

Benign

0.11

Polyphen

0.071

Vest4

0.065

MutPred

0.67

Gain of methylation at K314 (P = 0.0793);

MVP

0.61

MPC

0.18

ClinPred

0.019

GERP RS

5.4

Varity_R

0.12

gMVP

0.42

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