3-172633576-C-A

Variant names:

• chr3-172633576-C-A
• NM_020792.6:c.1126G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020792.6(NCEH1):​c.1126G>T​(p.Gly376Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCEH1 NM_020792.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97

Genes affected

NCEH1 (HGNC:29260): (neutral cholesterol ester hydrolase 1) Predicted to enable hydrolase activity. Predicted to be involved in ether lipid metabolic process. Predicted to act upstream of or within SMAD protein signal transduction; protein dephosphorylation; and xenobiotic metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20034027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCEH1	NM_020792.6	c.1126G>T	p.Gly376Cys	missense_variant	Exon 5 of 5	ENST00000475381.7	NP_065843.4
NCEH1	NM_001146276.3	c.1150G>T	p.Gly384Cys	missense_variant	Exon 5 of 5		NP_001139748.2
NCEH1	NM_001146277.3	c.727G>T	p.Gly243Cys	missense_variant	Exon 5 of 5		NP_001139749.1
NCEH1	NM_001146278.3	c.727G>T	p.Gly243Cys	missense_variant	Exon 4 of 4		NP_001139750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCEH1	ENST00000475381.7	c.1126G>T	p.Gly376Cys	missense_variant	Exon 5 of 5	1	NM_020792.6	ENSP00000418571.4
NCEH1	ENST00000538775.5	c.1246G>T	p.Gly416Cys	missense_variant	Exon 5 of 5	2		ENSP00000442464.1
NCEH1	ENST00000543711.5	c.727G>T	p.Gly243Cys	missense_variant	Exon 4 of 4	2		ENSP00000443227.1
NCEH1	ENST00000470419.1	n.*199G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1246G>T (p.G416C) alteration is located in exon 5 (coding exon 5) of the NCEH1 gene. This alteration results from a G to T substitution at nucleotide position 1246, causing the glycine (G) at amino acid position 416 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.;.
Eigen	Benign	0.019
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.5	.;D;D
REVEL	Benign	0.14
Sift	Benign	0.083	.;T;T
Sift4G	Benign	0.072	T;T;T
Vest4		0.12
MVP		0.33
MPC		0.39
ClinPred		0.94	D
GERP RS		4.8
gMVP		0.95

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-172351366;