8-66457104-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_144650.3(ADHFE1):c.1100C>T(p.Ala367Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
ADHFE1
NM_144650.3 missense
NM_144650.3 missense
Scores
7
7
5
Clinical Significance
Conservation
PhyloP100: 7.81
Genes affected
ADHFE1 (HGNC:16354): (alcohol dehydrogenase iron containing 1) The ADHFE1 gene encodes hydroxyacid-oxoacid transhydrogenase (EC 1.1.99.24), which is responsible for the oxidation of 4-hydroxybutyrate in mammalian tissues (Kardon et al., 2006 [PubMed 16616524]).[supplied by OMIM, Mar 2008]
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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 | UniProt |
---|---|---|---|---|---|---|---|
ADHFE1 | NM_144650.3 | c.1100C>T | p.Ala367Val | missense_variant | 12/14 | ENST00000396623.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADHFE1 | ENST00000396623.8 | c.1100C>T | p.Ala367Val | missense_variant | 12/14 | 1 | NM_144650.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251312Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135816
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GnomAD4 exome AF: 0.000144 AC: 210AN: 1461630Hom.: 0 Cov.: 30 AF XY: 0.000139 AC XY: 101AN XY: 727136
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74466
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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 | Dec 13, 2021 | The c.1100C>T (p.A367V) alteration is located in exon 12 (coding exon 12) of the ADHFE1 gene. This alteration results from a C to T substitution at nucleotide position 1100, causing the alanine (A) at amino acid position 367 to be replaced by a valine (V). 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
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;T
Polyphen
D;.
Vest4
MutPred
Loss of loop (P = 0.0804);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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