Genetic Variant NM_001013579.3:c.796G>A (chrX-70239898-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_001013579.3(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
NM_001013579.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.65

Publications

0 publications found

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:

ENSG00000294004 (HGNC:):

ENSG00000294004 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2349592.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013579.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AWAT1	NM_001013579.3	MANE Select	c.796G>A	p.Gly266Arg	missense	Exon 6 of 7	NP_001013597.1	Q58HT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AWAT1	ENST00000374521.4	TSL:1 MANE Select	c.796G>A	p.Gly266Arg	missense	Exon 6 of 7	ENSP00000363645.3	Q58HT5
ENSG00000294004	ENST00000720464.1		n.136+12524C>T		intron	N/A
ENSG00000294004	ENST00000720465.1		n.88+12524C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000306

AC:

AN:

111018

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000383

AC:

AN:

182939

AF XY:

0.000444

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 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

African (AFR)

AF:

0.00

AC:

AN:

26394

American (AMR)

AF:

0.0000568

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.000111

AC:

AN:

54117

European-Finnish (FIN)

AF:

0.000346

AC:

AN:

40406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3974

European-Non Finnish (NFE)

AF:

0.000571

AC:

481

AN:

841653

Other (OTH)

AF:

0.000608

AC:

AN:

46052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000306

AC:

AN:

111071

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

33291

show subpopulations

African (AFR)

AF:

0.0000327

AC:

AN:

30579

American (AMR)

AF:

0.0000959

AC:

AN:

10423

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2631

East Asian (EAS)

AF:

0.00

AC:

AN:

3502

South Asian (SAS)

AF:

0.00

AC:

AN:

2586

European-Finnish (FIN)

AF:

0.000672

AC:

AN:

5953

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000509

AC:

AN:

53008

Other (OTH)

AF:

0.00

AC:

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000625

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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

(source)

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

PhyloP100

7.6

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

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over