3-172633735-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020792.6(NCEH1):c.967C>T(p.Arg323Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
NCEH1
NM_020792.6 missense
NM_020792.6 missense
Scores
2
7
7
Clinical Significance
Conservation
PhyloP100: 2.17
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36677408).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCEH1 | NM_020792.6 | c.967C>T | p.Arg323Cys | missense_variant | 5/5 | ENST00000475381.7 | |
NCEH1 | NM_001146276.3 | c.991C>T | p.Arg331Cys | missense_variant | 5/5 | ||
NCEH1 | NM_001146277.3 | c.568C>T | p.Arg190Cys | missense_variant | 5/5 | ||
NCEH1 | NM_001146278.3 | c.568C>T | p.Arg190Cys | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCEH1 | ENST00000475381.7 | c.967C>T | p.Arg323Cys | missense_variant | 5/5 | 1 | NM_020792.6 | P1 | |
NCEH1 | ENST00000538775.5 | c.1087C>T | p.Arg363Cys | missense_variant | 5/5 | 2 | |||
NCEH1 | ENST00000543711.5 | c.568C>T | p.Arg190Cys | missense_variant | 4/4 | 2 | |||
NCEH1 | ENST00000470419.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251444Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135898
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727248
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74334
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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 | Jul 08, 2022 | The c.1087C>T (p.R363C) 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 1087, causing the arginine (R) at amino acid position 363 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Pathogenic
D;D;D
Vest4
MVP
MPC
1.2
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at