8-66454139-A-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.968A>T(p.Asn323Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,614,188 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000048 ( 1 hom. )
Consequence
ADHFE1
NM_144650.3 missense
NM_144650.3 missense
Scores
9
6
4
Clinical Significance
Conservation
PhyloP100: 9.29
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.968A>T | p.Asn323Ile | missense_variant | 10/14 | ENST00000396623.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADHFE1 | ENST00000396623.8 | c.968A>T | p.Asn323Ile | missense_variant | 10/14 | 1 | NM_144650.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000466 AC: 71AN: 152230Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000956 AC: 24AN: 251142Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135730
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461840Hom.: 1 Cov.: 30 AF XY: 0.0000454 AC XY: 33AN XY: 727222
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GnomAD4 genome AF: 0.000473 AC: 72AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29AN XY: 74502
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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 | Sep 14, 2022 | The c.968A>T (p.N323I) alteration is located in exon 10 (coding exon 10) of the ADHFE1 gene. This alteration results from a A to T substitution at nucleotide position 968, causing the asparagine (N) at amino acid position 323 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
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
Uncertain
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
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