Variant X-70041891-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001002254.1(AWAT2):c.919T>C(p.Tyr307His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,208,616 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000065 ( 0 hom. 28 hem. )

Consequence

AWAT2
NM_001002254.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.59

Variant links:

Genes affected

AWAT2 (HGNC:23251): (acyl-CoA wax alcohol acyltransferase 2) This gene encodes an enzyme belonging to the diacylglycerol acyltransferase family. This enzyme produces wax esters by the esterification of long chain (or wax) alcohols with acyl-CoA-derived fatty acids. It functions in lipid metabolism in the skin, mostly in undifferentiated peripheral sebocytes. This enzyme may also have acyl-CoA:retinol acyltransferase activities, where it catalyzes the synthesis of diacylglycerols and retinyl esters. [provided by RefSeq, May 2010]

AWAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20384869).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AWAT2	NM_001002254.1 linkuse as main transcript	c.919T>C	p.Tyr307His	missense_variant	7/8	ENST00000276101.7	NP_001002254.1
AWAT2	XM_011530876.3 linkuse as main transcript	c.919T>C	p.Tyr307His	missense_variant	7/8		XP_011529178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AWAT2	ENST00000276101.7 linkuse as main transcript	c.919T>C	p.Tyr307His	missense_variant	7/8	5	NM_001002254.1	ENSP00000421172	P1
AWAT2	ENST00000440401.1 linkuse as main transcript	c.*224T>C		3_prime_UTR_variant, NMD_transcript_variant	4/5	5		ENSP00000427523

Frequencies

GnomAD3 genomes

AF:

0.0000984

AC:

AN:

111739

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33911

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00341

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000158

AC:

AN:

183348

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

67814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00361

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000647

AC:

AN:

1096877

Hom.:

Cov.:

AF XY:

0.0000773

AC XY:

AN XY:

362259

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00305

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000595

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.0000984

AC:

AN:

111739

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33911

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00341

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000156

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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 30, 2023

The c.919T>C (p.Y307H) alteration is located in exon 7 (coding exon 7) of the AWAT2 gene. This alteration results from a T to C substitution at nucleotide position 919, causing the tyrosine (Y) at amino acid position 307 to be replaced by a histidine (H). 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

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.042

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

3.9

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.80

MVP

0.74

MPC

1.2

ClinPred

0.50

GERP RS

3.6

Varity_R

0.67

gMVP

0.99

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