Variant chr4-99216262-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001102470.2(ADH6):c.19G>T(p.Val7Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000427 in 1,404,684 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

ADH6
NM_001102470.2 missense, splice_region

Scores

Splicing: ADA: 0.9904

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

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]

ADH6 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADH6	NM_001102470.2 linkuse as main transcript	c.19G>T	p.Val7Phe	missense_variant, splice_region_variant	2/9	ENST00000394899.6
LOC100507053	NR_037884.1 linkuse as main transcript	n.3789+11831C>A		intron_variant, non_coding_transcript_variant
ADH6	NM_000672.4 linkuse as main transcript	c.19G>T	p.Val7Phe	missense_variant, splice_region_variant	2/8
ADH6	NR_132990.2 linkuse as main transcript	n.113G>T		splice_region_variant, non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH6	ENST00000394899.6 linkuse as main transcript	c.19G>T	p.Val7Phe	missense_variant, splice_region_variant	2/9	2	NM_001102470.2	P1	P28332-2
	ENST00000500358.6 linkuse as main transcript	n.3789+11831C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000427

AC:

AN:

1404684

Hom.:

Cov.:

AF XY:

0.00000430

AC XY:

AN XY:

698420

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:

0.00000553

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

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 submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.19G>T (p.V7F) alteration is located in exon 2 (coding exon 2) of the ADH6 gene. This alteration results from a G to T substitution at nucleotide position 19, causing the valine (V) at amino acid position 7 to be replaced by a phenylalanine (F). 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

0.19

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.082

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.6

D;D;D;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.036

D;D;D;.

Polyphen

0.97, 1.0

.;D;D;.

Vest4

0.59

MutPred

0.45

Loss of glycosylation at T3 (P = 0.0424);Loss of glycosylation at T3 (P = 0.0424);Loss of glycosylation at T3 (P = 0.0424);Loss of glycosylation at T3 (P = 0.0424);

MVP

0.55

MPC

0.44

ClinPred

0.99

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.89

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over