chrX-70234760-A-G

Variant names:

• chrX-70234760-A-G
• rs758323559
• NM_001013579.3:c.65A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001013579.3(AWAT1):​c.65A>G​(p.Tyr22Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,490 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: AWAT1 NM_001013579.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97
• Publications: 0 publications found

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]

ENSG00000294004 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.65A>G	p.Tyr22Cys	missense	Exon 1 of 7	NP_001013597.1	Q58HT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AWAT1	ENST00000374521.4	TSL:1 MANE Select	c.65A>G	p.Tyr22Cys	missense	Exon 1 of 7	ENSP00000363645.3	Q58HT5
	AWAT1	ENST00000480702.1	TSL:3	n.106A>G		non_coding_transcript_exon	Exon 1 of 4
	ENSG00000294004	ENST00000720464.1		n.136+17662T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000547 AC: 1 AN: 182782 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095490 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 360968

African (AFR) AF: 0.00 AC: 0 AN: 26362

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19367

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30190

South Asian (SAS) AF: 0.00 AC: 0 AN: 54060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839821

Other (OTH) AF: 0.00 AC: 0 AN: 46011

GnomAD4 genome Cov.: 21

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.63		Gain of catalytic residue at L23 (P = 0.138)
MVP		0.95
MPC		0.76
ClinPred		0.92	D
GERP RS		4.0
PromoterAI		0.044	Neutral
Varity_R		0.42
gMVP		0.92
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs758323559; hg19: chrX-69454610;