Variant 19-10548983-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

ATG4D links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.42 with no splicing effect.

BA1

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	Protein	UniProt
ATG4D	NM_032885.6 linkuse as main transcript	c.915C>T	p.Pro305=	synonymous_variant	6/10	ENST00000309469.9	NP_116274.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG4D	ENST00000309469.9 linkuse as main transcript	c.915C>T	p.Pro305=	synonymous_variant	6/10	1	NM_032885.6	ENSP00000311318	P1	Q86TL0-1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20318

AN:

151872

Hom.:

1463

Cov.:

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.:

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

AF:

0.134

AC:

20333

AN:

151990

Hom.:

1462

Cov.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over