4-99210167-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001102470.2(ADH6):c.482T>C(p.Ile161Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ADH6
NM_001102470.2 missense
NM_001102470.2 missense
Scores
4
4
11
Clinical Significance
Conservation
PhyloP100: 5.20
Publications
0 publications found
Genes affected
ADH6 (HGNC:255): (alcohol dehydrogenase 6 (class V)) This gene encodes class V alcohol dehydrogenase, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This gene is expressed in the stomach as well as in the liver, and it contains a glucocorticoid response element upstream of its 5' UTR, which is a steroid hormone receptor binding site. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.909
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ADH6 | NM_001102470.2 | c.482T>C | p.Ile161Thr | missense_variant | Exon 5 of 9 | ENST00000394899.6 | NP_001095940.1 | |
| ADH6 | NM_000672.4 | c.482T>C | p.Ile161Thr | missense_variant | Exon 5 of 8 | NP_000663.1 | ||
| LOC100507053 | NR_037884.1 | n.3789+5736A>G | intron_variant | Intron 4 of 9 | ||||
| ADH6 | NR_132990.2 | n.302+248T>C | intron_variant | Intron 3 of 6 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152176
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461550Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727088 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461550
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
727088
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33458
American (AMR)
AF:
AC:
0
AN:
44670
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26124
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
53374
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111822
Other (OTH)
AF:
AC:
0
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152176
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74344
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41444
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Mar 19, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.482T>C (p.I161T) alteration is located in exon 5 (coding exon 5) of the ADH6 gene. This alteration results from a T to C substitution at nucleotide position 482, causing the isoleucine (I) at amino acid position 161 to be replaced by a threonine (T). 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
Benign
DANN
Benign
DEOGEN2
Benign
.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;.
Polyphen
0.99, 0.52
.;D;P;.
Vest4
MutPred
Loss of stability (P = 0.0311);Loss of stability (P = 0.0311);Loss of stability (P = 0.0311);.;
MVP
MPC
0.54
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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