Menu
GeneBe

rs2304165

chr19-10548983-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_032885.6(ATG4D):c.915C>T(p.Pro305=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,798 control chromosomes in the GnomAD database, including 16,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1462 hom., cov: 31)
Exomes 𝑓: 0.14 ( 14989 hom. )

Consequence

ATG4D
NM_032885.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.42
Variant links:
Genes affected
ATG4D (HGNC:20789): (autophagy related 4D cysteine peptidase) Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene belongs to the autophagy-related protein 4 (Atg4) family of C54 endopeptidases. Members of this family encode proteins that play a role in the biogenesis of autophagosomes, which sequester the cytosol and organelles for degradation by lysosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-10548983-C-T is Benign according to our data. Variant chr19-10548983-C-T is described in ClinVar as [Benign]. Clinvar id is 1290655.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.42 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATG4DNM_032885.6 linkuse as main transcriptc.915C>T p.Pro305= synonymous_variant 6/10 ENST00000309469.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATG4DENST00000309469.9 linkuse as main transcriptc.915C>T p.Pro305= synonymous_variant 6/101 NM_032885.6 P1Q86TL0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.134
AC:
20318
AN:
151872
Hom.:
1463
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.114
Gnomad AMI
AF:
0.343
Gnomad AMR
AF:
0.122
Gnomad ASJ
AF:
0.103
Gnomad EAS
AF:
0.119
Gnomad SAS
AF:
0.181
Gnomad FIN
AF:
0.160
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.140
Gnomad OTH
AF:
0.142
GnomAD3 exomes
AF:
0.135
AC:
33932
AN:
251292
Hom.:
2472
AF XY:
0.140
AC XY:
18993
AN XY:
135828
show subpopulations
Gnomad AFR exome
AF:
0.112
Gnomad AMR exome
AF:
0.106
Gnomad ASJ exome
AF:
0.0953
Gnomad EAS exome
AF:
0.125
Gnomad SAS exome
AF:
0.187
Gnomad FIN exome
AF:
0.141
Gnomad NFE exome
AF:
0.137
Gnomad OTH exome
AF:
0.144
GnomAD4 exome
AF:
0.141
AC:
206075
AN:
1461808
Hom.:
14989
Cov.:
32
AF XY:
0.142
AC XY:
103428
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.114
Gnomad4 AMR exome
AF:
0.107
Gnomad4 ASJ exome
AF:
0.0981
Gnomad4 EAS exome
AF:
0.105
Gnomad4 SAS exome
AF:
0.183
Gnomad4 FIN exome
AF:
0.138
Gnomad4 NFE exome
AF:
0.142
Gnomad4 OTH exome
AF:
0.141
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.134
AC:
20333
AN:
151990
Hom.:
1462
Cov.:
31
AF XY:
0.137
AC XY:
10178
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.114
Gnomad4 AMR
AF:
0.122
Gnomad4 ASJ
AF:
0.103
Gnomad4 EAS
AF:
0.119
Gnomad4 SAS
AF:
0.181
Gnomad4 FIN
AF:
0.160
Gnomad4 NFE
AF:
0.140
Gnomad4 OTH
AF:
0.142
Alfa
AF:
0.137
Hom.:
1939
Bravo
AF:
0.130
Asia WGS
AF:
0.157
AC:
546
AN:
3478
EpiCase
AF:
0.145
EpiControl
AF:
0.146

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 14, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
1.5
Dann
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2304165; hg19: chr19-10659659; COSMIC: COSV57264690; COSMIC: COSV57264690; API