X-70237174-G-C

Variant names:

• chrX-70237174-G-C
• rs747448909
• NM_001013579.3:c.386G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001013579.3(AWAT1):​c.386G>C​(p.Gly129Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G129V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: AWAT1 NM_001013579.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.57
• Publications: 1 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

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.386G>C	p.Gly129Ala	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.386G>C	p.Gly129Ala	missense	Exon 4 of 7	ENSP00000363645.3	Q58HT5
	AWAT1	ENST00000480702.1	TSL:3	n.427G>C		non_coding_transcript_exon	Exon 4 of 4
	ENSG00000294004	ENST00000720464.1		n.136+15248C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 110631 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 110631 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 32859

African (AFR) AF: 0.00 AC: 0 AN: 30365

American (AMR) AF: 0.00 AC: 0 AN: 10408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3490

South Asian (SAS) AF: 0.00 AC: 0 AN: 2573

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52843

Other (OTH) AF: 0.00 AC: 0 AN: 1492

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		9.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.35
Sift	Benign	0.035	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.84		Loss of ubiquitination at K125 (P = 0.0702)
MVP		0.71
MPC		0.59
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.65
gMVP		0.79
Mutation Taster		=80/20	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: rs747448909; hg19: chrX-69457024;