X-70235788-C-G

Variant names:

• chrX-70235788-C-G
• rs781197090
• NM_001013579.3:c.149C>G

Variant summary

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

The NM_001013579.3(AWAT1):​c.149C>G​(p.Ala50Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A50V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: AWAT1 NM_001013579.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• 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=0.357903).

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.149C>G	p.Ala50Gly	missense	Exon 2 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.149C>G	p.Ala50Gly	missense	Exon 2 of 7	ENSP00000363645.3	Q58HT5
	AWAT1	ENST00000480702.1	TSL:3	n.190C>G		non_coding_transcript_exon	Exon 2 of 4
	ENSG00000294004	ENST00000720464.1		n.136+16634G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.14
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.032
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.19	T
Polyphen		0.32	B
Vest4		0.23
MutPred		0.61		Loss of stability (P = 0.0277)
MVP		0.71
MPC		0.23
ClinPred		0.61	D
GERP RS		-2.1
Varity_R		0.47
gMVP		0.53
Mutation Taster		=98/2	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: rs781197090; hg19: chrX-69455638;