chrX-70238334-C-A

Variant names:

• chrX-70238334-C-A
• rs761946612
• NM_001013579.3:c.583C>A

Variant summary

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

The NM_001013579.3(AWAT1):​c.583C>A​(p.Leu195Ile) 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 1,095,268 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: 23)
  • 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: 0.558
• 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.583C>A	p.Leu195Ile	missense	Exon 5 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.583C>A	p.Leu195Ile	missense	Exon 5 of 7	ENSP00000363645.3	Q58HT5
	ENSG00000294004	ENST00000720464.1		n.136+14088G>T		intron	N/A
	ENSG00000294004	ENST00000720465.1		n.88+14088G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095268 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 360906

African (AFR) AF: 0.00 AC: 0 AN: 26364

American (AMR) AF: 0.00 AC: 0 AN: 35130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19342

East Asian (EAS) AF: 0.00 AC: 0 AN: 30097

South Asian (SAS) AF: 0.00 AC: 0 AN: 53891

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40435

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4115

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839925

Other (OTH) AF: 0.00 AC: 0 AN: 45969

GnomAD4 genome Cov.: 23

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	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.56
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.10	T
Polyphen		0.96	D
Vest4		0.44
MutPred		0.79		Gain of methylation at K199 (P = 0.1061)
MVP		0.54
MPC		0.55
ClinPred		0.76	D
GERP RS		4.9
Varity_R		0.23
gMVP		0.30
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761946612; hg19: chrX-69458184;