Genetic Variant NCEH1:p.Arg245Cys (chr3-172633969-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020792.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCEH1	NM_020792.6	MANE Select	c.733C>T	p.Arg245Cys	missense	Exon 5 of 5	NP_065843.4
NCEH1	NM_001146276.3		c.757C>T	p.Arg253Cys	missense	Exon 5 of 5	NP_001139748.2	Q6PIU2-2
NCEH1	NM_001146277.3		c.334C>T	p.Arg112Cys	missense	Exon 5 of 5	NP_001139749.1	Q6PIU2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCEH1	ENST00000475381.7	TSL:1 MANE Select	c.733C>T	p.Arg245Cys	missense	Exon 5 of 5	ENSP00000418571.4	Q6PIU2-1
NCEH1	ENST00000538775.5	TSL:2	c.853C>T	p.Arg285Cys	missense	Exon 5 of 5	ENSP00000442464.1	A0A0A0MTJ9
NCEH1	ENST00000894447.1		c.727C>T	p.Arg243Cys	missense	Exon 5 of 5	ENSP00000564506.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251466

AF XY:

0.0000147

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 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

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

1112010

Other (OTH)

AF:

0.0000331

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.74

PhyloP100

7.7

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.59

MVP

0.55

MPC

1.3

ClinPred

1.0

GERP RS

5.7

gMVP

0.78

Mutation Taster

=37/63

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over