Variant 3-172633969-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020792.6(NCEH1):c.733C>T(p.Arg245Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

NCEH1
NM_020792.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

Variant links:

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]

NCEH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NCEH1	NM_020792.6 linkuse as main transcript	c.733C>T	p.Arg245Cys	missense_variant	5/5	ENST00000475381.7
NCEH1	NM_001146276.3 linkuse as main transcript	c.757C>T	p.Arg253Cys	missense_variant	5/5
NCEH1	NM_001146277.3 linkuse as main transcript	c.334C>T	p.Arg112Cys	missense_variant	5/5
NCEH1	NM_001146278.3 linkuse as main transcript	c.334C>T	p.Arg112Cys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCEH1	ENST00000475381.7 linkuse as main transcript	c.733C>T	p.Arg245Cys	missense_variant	5/5	1	NM_020792.6	P1	Q6PIU2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251466

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2021

The c.853C>T (p.R285C) alteration is located in exon 5 (coding exon 5) of the NCEH1 gene. This alteration results from a C to T substitution at nucleotide position 853, causing the arginine (R) at amino acid position 285 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

Benign

0.32

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.14

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;.;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-0.74

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.60

REVEL

Uncertain

0.60

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.59

MVP

0.55

MPC

1.3

ClinPred

1.0

GERP RS

5.7

gMVP

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over