X-70237215-A-T

Variant names:

• chrX-70237215-A-T
• NM_001013579.3:c.427A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001013579.3(AWAT1):​c.427A>T​(p.Ile143Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: AWAT1 NM_001013579.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.25
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33316958).

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.427A>T	p.Ile143Phe	missense	Exon 4 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.427A>T	p.Ile143Phe	missense	Exon 4 of 7	ENSP00000363645.3	Q58HT5
	AWAT1	ENST00000480702.1	TSL:3	n.468A>T		non_coding_transcript_exon	Exon 4 of 4
	ENSG00000294004	ENST00000720464.1		n.136+15207T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 21

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	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.034
Sift	Benign	0.087	T
Sift4G	Benign	0.068	T
Polyphen		0.17	B
Vest4		0.53
MutPred		0.48		Gain of ubiquitination at K142 (P = 0.1128)
MVP		0.74
MPC		0.62
ClinPred		0.44	T
GERP RS		0.49
Varity_R		0.14
gMVP		0.60
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

hg19: chrX-69457065;