4-99208796-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001102470.2(ADH6):​c.700C>A​(p.Gln234Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

ADH6
NM_001102470.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022165865).
BP6
Variant 4-99208796-G-T is Benign according to our data. Variant chr4-99208796-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2488566.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADH6NM_001102470.2 linkuse as main transcriptc.700C>A p.Gln234Lys missense_variant 6/9 ENST00000394899.6 NP_001095940.1 P28332-2Q8IUN7
ADH6NM_000672.4 linkuse as main transcriptc.700C>A p.Gln234Lys missense_variant 6/8 NP_000663.1 P28332-1Q8IUN7
ADH6NR_132990.2 linkuse as main transcriptn.435C>A non_coding_transcript_exon_variant 4/7
LOC100507053NR_037884.1 linkuse as main transcriptn.3789+4365G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADH6ENST00000394899.6 linkuse as main transcriptc.700C>A p.Gln234Lys missense_variant 6/92 NM_001102470.2 ENSP00000378359.2 P28332-2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152000
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251278
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135806
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152000
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74218
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 23, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.26
DANN
Benign
0.54
DEOGEN2
Benign
0.0074
.;.;T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0026
N
LIST_S2
Benign
0.54
T;T;T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.022
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-2.1
.;N;N;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
3.1
N;N;N;N
REVEL
Benign
0.042
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;.
Polyphen
0.0
.;B;B;.
Vest4
0.13
MVP
0.17
MPC
0.12
ClinPred
0.048
T
GERP RS
-1.0
Varity_R
0.033
gMVP
0.56

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.

Other links and lift over

dbSNP: rs140015086; hg19: chr4-100129953; API