Variant X-70240176-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001013579.3(AWAT1):c.873C>T(p.Ser291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,209,542 control chromosomes in the GnomAD database, including 20 homozygotes. There are 1,120 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., 79 hem., cov: 24)

Exomes 𝑓: 0.0029 ( 19 hom. 1041 hem. )

Consequence

AWAT1
NM_001013579.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.802

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 Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant X-70240176-C-T is Benign according to our data. Variant chrX-70240176-C-T is described in ClinVar as [Benign]. Clinvar id is 731070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.802 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00287 (3153/1097719) while in subpopulation MID AF= 0.0249 (103/4136). AF 95% confidence interval is 0.021. There are 19 homozygotes in gnomad4_exome. There are 1041 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 79 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AWAT1	NM_001013579.3 linkuse as main transcript	c.873C>T	p.Ser291=	synonymous_variant	7/7	ENST00000374521.4	NP_001013597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AWAT1	ENST00000374521.4 linkuse as main transcript	c.873C>T	p.Ser291=	synonymous_variant	7/7	1	NM_001013579.3	ENSP00000363645	P1

Frequencies

GnomAD3 genomes

AF:

0.00241

AC:

269

AN:

111770

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

AN XY:

33950

show subpopulations

Gnomad AFR

AF:

0.000260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00172

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.000662

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00233

Gnomad OTH

AF:

0.00795

GnomAD3 exomes

AF:

0.00342

AC:

626

AN:

182797

Hom.:

AF XY:

0.00334

AC XY:

225

AN XY:

67359

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00190

Gnomad ASJ exome

AF:

0.0441

Gnomad EAS exome

AF:

0.000144

Gnomad SAS exome

AF:

0.00195

Gnomad FIN exome

AF:

0.000314

Gnomad NFE exome

AF:

0.00199

Gnomad OTH exome

AF:

0.00819

GnomAD4 exome

AF:

0.00287

AC:

3153

AN:

1097719

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

1041

AN XY:

363085

show subpopulations

Gnomad4 AFR exome

AF:

0.000720

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.0418

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.000642

Gnomad4 NFE exome

AF:

0.00213

Gnomad4 OTH exome

AF:

0.00529

GnomAD4 genome

AF:

0.00241

AC:

269

AN:

111823

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

AN XY:

34013

show subpopulations

Gnomad4 AFR

AF:

0.000259

Gnomad4 AMR

AF:

0.00171

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00113

Gnomad4 FIN

AF:

0.000662

Gnomad4 NFE

AF:

0.00233

Gnomad4 OTH

AF:

0.00785

Alfa

AF:

0.00760

Hom.:

Bravo

AF:

0.00235

EpiCase

AF:

0.00338

EpiControl

AF:

0.00238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.2

DANN

Benign

0.63

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