4-99207578-C-T

Variant names:

• chr4-99207578-C-T
• NM_001102470.2:c.832G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001102470.2(ADH6):​c.832G>A​(p.Ala278Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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)
• Consequence: ADH6 NM_001102470.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.993
• Publications: 0 publications found

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]

ENSG00000246090 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2417784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102470.2. 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
	ADH6	NM_001102470.2	MANE Select	c.832G>A	p.Ala278Thr	missense	Exon 7 of 9	NP_001095940.1	P28332-2
	ADH6	NM_000672.4		c.832G>A	p.Ala278Thr	missense	Exon 7 of 8	NP_000663.1	P28332-1
	ADH6	NR_132990.2		n.567G>A		non_coding_transcript_exon	Exon 5 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH6	ENST00000394899.6	TSL:2 MANE Select	c.832G>A	p.Ala278Thr	missense	Exon 7 of 9	ENSP00000378359.2	P28332-2
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+3147C>T		intron	N/A
	ADH6	ENST00000881183.1		c.853G>A	p.Ala285Thr	missense	Exon 7 of 9	ENSP00000551242.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.2
DANN	Uncertain	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.99
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.069
Sift	Benign	0.075	T
Sift4G	Benign	0.16	T
Polyphen		0.43	B
Vest4		0.13
MutPred		0.48		Loss of helix (P = 0.3949)
MVP		0.62
MPC		0.14
ClinPred		0.65	D
GERP RS		3.0
Varity_R		0.034
gMVP		0.44
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr4-100128735;