4-99419054-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000673.7(ADH7):​c.893C>T​(p.Ala298Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADH7
NM_000673.7 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.30
Variant links:
Genes affected
ADH7 (HGNC:256): (alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide) This gene encodes class IV alcohol dehydrogenase 7 mu or sigma subunit, 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. The enzyme encoded by this gene is inefficient in ethanol oxidation, but is the most active as a retinol dehydrogenase; thus it may participate in the synthesis of retinoic acid, a hormone important for cellular differentiation. The expression of this gene is much more abundant in stomach than liver, thus differing from the other known gene family members. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22810015).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADH7NM_000673.7 linkuse as main transcriptc.893C>T p.Ala298Val missense_variant 7/9 ENST00000437033.7
ADH7NM_001166504.2 linkuse as main transcriptc.953C>T p.Ala318Val missense_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADH7ENST00000437033.7 linkuse as main transcriptc.893C>T p.Ala298Val missense_variant 7/91 NM_000673.7 P1
ADH7ENST00000209665.8 linkuse as main transcriptc.929C>T p.Ala310Val missense_variant 7/91 P40394-1
ADH7ENST00000476959.5 linkuse as main transcriptc.953C>T p.Ala318Val missense_variant 7/92 P40394-2
ADH7ENST00000482593.5 linkuse as main transcriptc.722C>T p.Ala241Val missense_variant 8/103

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251054
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135670
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461578
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727092
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2021The c.929C>T (p.A310V) alteration is located in exon 7 (coding exon 7) of the ADH7 gene. This alteration results from a C to T substitution at nucleotide position 929, causing the alanine (A) at amino acid position 310 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
ADH7-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 18, 2024The ADH7 c.953C>T variant is predicted to result in the amino acid substitution p.Ala318Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;T;.;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.21
T;T;T;T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.23
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;.;.;.
MutationTaster
Benign
0.89
N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-2.6
D;D;D;D
REVEL
Benign
0.093
Sift
Benign
0.10
T;T;D;T
Sift4G
Uncertain
0.053
T;T;T;T
Polyphen
0.18
B;.;.;.
Vest4
0.29
MutPred
0.62
Loss of ubiquitination at K311 (P = 0.0777);.;.;.;
MVP
0.44
MPC
0.022
ClinPred
0.78
D
GERP RS
4.5
Varity_R
0.24
gMVP
0.47

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: rs1433147867; hg19: chr4-100340211; API