Genetic Variant NM_032804.6:c.493G>A (chr10-62805552-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032804.6(ADO):c.493G>A(p.Val165Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,553,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

ADO
NM_032804.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.499

Publications

0 publications found

Variant links:

Genes affected

ADO (HGNC:23506): (2-aminoethanethiol dioxygenase) Human thiol dioxygenases include cysteine dioxygenase (CDO; MIM 603943) and cysteamine (2-aminoethanethiol) dioxygenase (ADO; EC 1.13.11.19). CDO adds 2 oxygen atoms to free cysteine, whereas ADO adds 2 oxygen atoms to free cysteamine to form hypotaurine (Dominy et al., 2007 [PubMed 17581819]).[supplied by OMIM, Mar 2008]

ADO links:

ENSG00000238280 (HGNC:):

ENSG00000238280 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03366068).

BS2

High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADO	NM_032804.6 link	c.493G>A	p.Val165Met	missense_variant	Exon 1 of 1	ENST00000373783.3	NP_116193.2	Q96SZ5B3KXN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADO	ENST00000373783.3 link	c.493G>A	p.Val165Met	missense_variant	Exon 1 of 1	6	NM_032804.6	ENSP00000362888.1		Q96SZ5

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000202

AC:

AN:

153314

AF XY:

0.000228

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000401

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000758

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000375

AC:

525

AN:

1401112

Hom.:

Cov.:

AF XY:

0.000373

AC XY:

258

AN XY:

691904

show subpopulations

African (AFR)

AF:

0.0000951

AC:

AN:

31538

American (AMR)

AF:

0.0000831

AC:

AN:

36102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25002

East Asian (EAS)

AF:

0.00

AC:

AN:

36570

South Asian (SAS)

AF:

0.00

AC:

AN:

79812

European-Finnish (FIN)

AF:

0.0000873

AC:

AN:

45816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.000467

AC:

506

AN:

1082498

Other (OTH)

AF:

0.000155

AC:

AN:

58096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000177

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.000208

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.000489

AC:

ExAC

AF:

0.000141

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.493G>A (p.V165M) alteration is located in exon 1 (coding exon 1) of the ADO gene. This alteration results from a G to A substitution at nucleotide position 493, causing the valine (V) at amino acid position 165 to be replaced by a methionine (M). 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

0.21

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0036

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.57

M_CAP

Benign

0.015

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.50

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.41

REVEL

Benign

0.17

Sift

Benign

0.064

Sift4G

Benign

0.062

Polyphen

0.95

Vest4

0.051

MVP

0.043

MPC

0.70

ClinPred

0.067

GERP RS

-8.7

Varity_R

0.064

gMVP

0.40

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over