Variant 8-66451957-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144650.3(ADHFE1):c.739G>T(p.Ala247Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000417 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ADHFE1
NM_144650.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.62

Variant links:

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]

ADHFE1 links:

ENSG00000285791 (HGNC:):

ENSG00000285791 links:

Genome browser will be placed here

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	Protein	UniProt
ADHFE1	NM_144650.3 link	c.739G>T	p.Ala247Ser	missense_variant	9/14	ENST00000396623.8	NP_653251.2	Q8IWW8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADHFE1	ENST00000396623.8 link	c.739G>T	p.Ala247Ser	missense_variant	9/14	1	NM_144650.3	ENSP00000379865.3		Q8IWW8-1
ENSG00000285791	ENST00000648156.1 link	n.595G>T		non_coding_transcript_exon_variant	7/20			ENSP00000497007.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250404

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461576

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727096

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000523

Hom.:

Bravo

AF:

0.00000378

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 14, 2024

The c.739G>T (p.A247S) alteration is located in exon 9 (coding exon 9) of the ADHFE1 gene. This alteration results from a G to T substitution at nucleotide position 739, causing the alanine (A) at amino acid position 247 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.23

Sift

Benign

0.46

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.44

B;.

Vest4

0.44

MVP

0.71

MPC

0.28

ClinPred

0.91

GERP RS

5.5

Varity_R

0.45

gMVP

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over