rs367986260

Variant names:

• chr3-172645627-T-A
• NM_020792.6:c.433A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-172645627-T-A
• chr3-172645627-T-C
• chr3-172645627-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020792.6(NCEH1):​c.433A>T​(p.Ile145Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I145V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NCEH1 NM_020792.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCEH1	NM_020792.6	c.433A>T	p.Ile145Phe	missense_variant	Exon 3 of 5	ENST00000475381.7	NP_065843.4
NCEH1	NM_001146276.3	c.457A>T	p.Ile153Phe	missense_variant	Exon 3 of 5		NP_001139748.2
NCEH1	NM_001146277.3	c.34A>T	p.Ile12Phe	missense_variant	Exon 3 of 5		NP_001139749.1
NCEH1	NM_001146278.3	c.34A>T	p.Ile12Phe	missense_variant	Exon 2 of 4		NP_001139750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCEH1	ENST00000475381.7	c.433A>T	p.Ile145Phe	missense_variant	Exon 3 of 5	1	NM_020792.6	ENSP00000418571.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440422 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 716996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	.;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.010	.;D;D
Sift4G	Benign	0.063	T;D;D
Vest4		0.85
MVP		0.60
MPC		1.3
ClinPred		0.98	D
GERP RS		2.6
gMVP		0.81

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: chr3-172363417;