rs1437389652

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_000671.4(ADH5):c.64A>G(p.Ile22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,554,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

ADH5
NM_000671.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Publications

0 publications found

Variant links:

Genes affected

ADH5 (HGNC:253): (alcohol dehydrogenase 5 (class III), chi polypeptide) This gene encodes 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 encoded protein forms a homodimer. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis. The human genome contains several non-transcribed pseudogenes related to this gene. [provided by RefSeq, Oct 2008]

ADH5 Gene-Disease associations (from GenCC):

AMED syndrome, digenic
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ADH5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.0261 (below the threshold of 3.09). Trascript score misZ: 1.5869 (below the threshold of 3.09). GenCC associations: The gene is linked to AMED syndrome, digenic.

BP4

Computational evidence support a benign effect (MetaRNN=0.1330533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH5	NM_000671.4	MANE Select	c.64A>G	p.Ile22Val	missense	Exon 2 of 9	NP_000662.3	P11766

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADH5	ENST00000296412.14	TSL:1 MANE Select	c.64A>G	p.Ile22Val	missense	Exon 2 of 9	ENSP00000296412.8	P11766
ADH5	ENST00000885760.1		c.64A>G	p.Ile22Val	missense	Exon 2 of 9	ENSP00000555819.1
ADH5	ENST00000929295.1		c.64A>G	p.Ile22Val	missense	Exon 2 of 9	ENSP00000599354.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

188268

AF XY:

0.0000198

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 FIN exome

AF:

0.0000519

Gnomad NFE exome

AF:

0.0000236

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1402368

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

693534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31884

American (AMR)

AF:

0.00

AC:

AN:

35122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24768

East Asian (EAS)

AF:

0.00

AC:

AN:

37886

South Asian (SAS)

AF:

0.0000131

AC:

AN:

76066

European-Finnish (FIN)

AF:

0.0000776

AC:

AN:

51514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

1081592

Other (OTH)

AF:

0.0000863

AC:

AN:

57930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.11

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0088

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.3

PhyloP100

2.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.81

REVEL

Benign

0.12

Sift

Benign

0.17

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.22

MutPred

0.48

Gain of ubiquitination at K18 (P = 0.0882)

MVP

0.15

MPC

0.22

ClinPred

0.049

GERP RS

4.0

PromoterAI

0.023

Neutral

(source)

Varity_R

0.16

gMVP

0.60

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over