4-99419019-T-C

Variant summary

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

The NM_000673.7(ADH7):ā€‹c.928A>Gā€‹(p.Thr310Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ADH7
NM_000673.7 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.130
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=0.15523717).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADH7NM_000673.7 linkuse as main transcriptc.928A>G p.Thr310Ala missense_variant 7/9 ENST00000437033.7 NP_000664.3 P40394
ADH7NM_001166504.2 linkuse as main transcriptc.988A>G p.Thr330Ala missense_variant 7/9 NP_001159976.1 P40394-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADH7ENST00000437033.7 linkuse as main transcriptc.928A>G p.Thr310Ala missense_variant 7/91 NM_000673.7 ENSP00000414254.2 A0A0C4DG85
ADH7ENST00000209665.8 linkuse as main transcriptc.964A>G p.Thr322Ala missense_variant 7/91 ENSP00000209665.4 P40394-1
ADH7ENST00000476959.5 linkuse as main transcriptc.988A>G p.Thr330Ala missense_variant 7/92 ENSP00000420269.1 P40394-2
ADH7ENST00000482593.5 linkuse as main transcriptc.757A>G p.Thr253Ala missense_variant 8/103 ENSP00000420613.1 E9PFG0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461574
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727088
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:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 29, 2024The c.964A>G (p.T322A) alteration is located in exon 7 (coding exon 7) of the ADH7 gene. This alteration results from a A to G substitution at nucleotide position 964, causing the threonine (T) at amino acid position 322 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
13
DANN
Benign
0.97
DEOGEN2
Benign
0.15
T;T;.;.
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.59
T;T;T;T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.9
L;.;.;.
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Benign
0.037
Sift
Benign
0.048
D;D;D;D
Sift4G
Uncertain
0.048
D;D;T;D
Polyphen
0.15
B;.;.;.
Vest4
0.17
MutPred
0.50
Loss of methylation at K327 (P = 0.0969);.;.;.;
MVP
0.19
MPC
0.077
ClinPred
0.77
D
GERP RS
0.43
Varity_R
0.31
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-100340176; API