4-99205018-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001102470.2(ADH6):​c.1010T>A​(p.Met337Lys) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ADH6
NM_001102470.2 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.53
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.2848739).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADH6NM_001102470.2 linkc.1010T>A p.Met337Lys missense_variant Exon 8 of 9 ENST00000394899.6 NP_001095940.1 P28332-2Q8IUN7
ADH6NM_000672.4 linkc.1010T>A p.Met337Lys missense_variant Exon 8 of 8 NP_000663.1 P28332-1Q8IUN7
ADH6NR_132990.2 linkn.745T>A non_coding_transcript_exon_variant Exon 6 of 7
LOC100507053NR_037884.1 linkn.3789+587A>T intron_variant Intron 4 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADH6ENST00000394899.6 linkc.1010T>A p.Met337Lys missense_variant Exon 8 of 9 2 NM_001102470.2 ENSP00000378359.2 P28332-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
11
DANN
Benign
0.79
DEOGEN2
Benign
0.20
.;T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.8
L;L
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-4.5
D;D
REVEL
Benign
0.086
Sift
Benign
0.13
T;T
Sift4G
Benign
0.070
T;T
Polyphen
0.28
B;B
Vest4
0.72
MutPred
0.51
Loss of catalytic residue at V333 (P = 0.0177);Loss of catalytic residue at V333 (P = 0.0177);
MVP
0.22
MPC
0.18
ClinPred
0.37
T
GERP RS
-0.66
Varity_R
0.11
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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.

Other links and lift over

dbSNP: rs1560803215; hg19: chr4-100126175; API