chr5-82178571-A-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_031482.5(ATG10):āc.437A>Gā(p.Asp146Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000559 in 1,608,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000057 ( 0 hom. )
Consequence
ATG10
NM_031482.5 missense
NM_031482.5 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.63
Genes affected
ATG10 (HGNC:20315): (autophagy related 10) Autophagy is a process for the bulk degradation of cytosolic compartments by lysosomes. ATG10 is an E2-like enzyme involved in 2 ubiquitin-like modifications essential for autophagosome formation: ATG12 (MIM 609608)-ATG5 (MIM 604261) conjugation and modification of a soluble form of MAP-LC3 (MAP1LC3A; MIM 601242), a homolog of yeast Apg8, to a membrane-bound form (Nemoto et al., 2003 [PubMed 12890687]).[supplied by OMIM, Mar 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042250156).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATG10 | NM_031482.5 | c.437A>G | p.Asp146Gly | missense_variant | 5/8 | ENST00000282185.8 | NP_113670.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATG10 | ENST00000282185.8 | c.437A>G | p.Asp146Gly | missense_variant | 5/8 | 1 | NM_031482.5 | ENSP00000282185 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152098Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
7
AN:
152098
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000148 AC: 37AN: 250232Hom.: 0 AF XY: 0.000237 AC XY: 32AN XY: 135250
GnomAD3 exomes
AF:
AC:
37
AN:
250232
Hom.:
AF XY:
AC XY:
32
AN XY:
135250
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000570 AC: 83AN: 1456548Hom.: 0 Cov.: 28 AF XY: 0.0000786 AC XY: 57AN XY: 725030
GnomAD4 exome
AF:
AC:
83
AN:
1456548
Hom.:
Cov.:
28
AF XY:
AC XY:
57
AN XY:
725030
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74300
GnomAD4 genome
AF:
AC:
7
AN:
152098
Hom.:
Cov.:
32
AF XY:
AC XY:
7
AN XY:
74300
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
21
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 | Mar 08, 2024 | The c.437A>G (p.D146G) alteration is located in exon 6 (coding exon 4) of the ATG10 gene. This alteration results from a A to G substitution at nucleotide position 437, causing the aspartic acid (D) at amino acid position 146 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Gain of catalytic residue at I148 (P = 0.1482);Gain of catalytic residue at I148 (P = 0.1482);Gain of catalytic residue at I148 (P = 0.1482);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at