X-70237159-C-T

Variant names:

• chrX-70237159-C-T
• rs752895931
• NM_001013579.3:c.371C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013579.3(AWAT1):​c.371C>T​(p.Ser124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,094,933 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: AWAT1 NM_001013579.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0860
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17559704).

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.371C>T	p.Ser124Leu	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.371C>T	p.Ser124Leu	missense	Exon 4 of 7	ENSP00000363645.3	Q58HT5
	AWAT1	ENST00000480702.1	TSL:3	n.412C>T		non_coding_transcript_exon	Exon 4 of 4
	ENSG00000294004	ENST00000720464.1		n.136+15263G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1094933 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1 AN XY: 360547

African (AFR) AF: 0.00 AC: 0 AN: 26377

American (AMR) AF: 0.00 AC: 0 AN: 34945

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19321

East Asian (EAS) AF: 0.00 AC: 0 AN: 30141

South Asian (SAS) AF: 0.00 AC: 0 AN: 53189

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 840461

Other (OTH) AF: 0.00 AC: 0 AN: 46002

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.16
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.086
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.082
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.018	D
Polyphen		0.040	B
Vest4		0.15
MutPred		0.55		Loss of glycosylation at S124 (P = 0.0201)
MVP		0.77
MPC		0.15
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.36
gMVP		0.76
Mutation Taster		=94/6	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: rs752895931; hg19: chrX-69457009;