chr10-62805552-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032804.6(ADO):​c.493G>C​(p.Val165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V165M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ADO
NM_032804.6 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03216195).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADONM_032804.6 linkc.493G>C p.Val165Leu 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
ADOENST00000373783.3 linkc.493G>C p.Val165Leu missense_variant Exon 1 of 1 6 NM_032804.6 ENSP00000362888.1 Q96SZ5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000652
AC:
1
AN:
153314
AF XY:
0.0000120
show subpopulations
Gnomad AFR exome
AF:
0.000130
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.14e-7
AC:
1
AN:
1401112
Hom.:
0
Cov.:
34
AF XY:
0.00000145
AC XY:
1
AN XY:
691904
show subpopulations
African (AFR)
AF:
0.0000317
AC:
1
AN:
31538
American (AMR)
AF:
0.00
AC:
0
AN:
36102
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25002
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36570
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79812
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45816
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5678
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1082498
Other (OTH)
AF:
0.00
AC:
0
AN:
58096
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.20
DANN
Benign
0.75
DEOGEN2
Benign
0.0011
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.032
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.74
N
PhyloP100
-0.50
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
0.29
N
REVEL
Benign
0.069
Sift
Benign
0.88
T
Sift4G
Benign
0.80
T
Polyphen
0.0010
B
Vest4
0.028
MutPred
0.57
Gain of helix (P = 0.0696);
MVP
0.043
MPC
0.63
ClinPred
0.49
T
GERP RS
-8.7
Varity_R
0.056
gMVP
0.44
Mutation Taster
=87/13
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

Publications

Other links and lift over

dbSNP: rs202015367; hg19: chr10-64565312; API