8-66432533-G-A

Position:

• chr8-66432533-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144650.3(ADHFE1):​c.17G>A​(p.Arg6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADHFE1 NM_144650.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00

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]

ACMG classification

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=0.42180544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADHFE1	NM_144650.3	c.17G>A	p.Arg6Gln	missense_variant	1/14	ENST00000396623.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADHFE1	ENST00000396623.8	c.17G>A	p.Arg6Gln	missense_variant	1/14	1	NM_144650.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1207764 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 585682

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: 0.00

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.94	D;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.11
Sift	Benign	0.042	D
Sift4G	Benign	0.23	T
Polyphen		0.99	D
Vest4		0.36
MutPred		0.31		Loss of methylation at R6 (P = 0.002);
MVP		0.28
MPC		0.061
ClinPred		0.60	D
GERP RS		3.1
Varity_R		0.063
gMVP		0.60

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: chr8-67344768;