Variant 1-62829046-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032852.4(ATG4C):c.803A>T(p.Asn268Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ATG4C
NM_032852.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.688

Variant links:

Genes affected

ATG4C (HGNC:16040): (autophagy related 4C 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 encodes a member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of cysteine proteases. Alternate transcriptional splice variants, encoding the same protein, have been characterized. [provided by RefSeq, Jul 2008]

ATG4C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09643328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG4C	NM_032852.4 linkuse as main transcript	c.803A>T	p.Asn268Ile	missense_variant	7/11	ENST00000317868.9	NP_116241.2	Q96DT6A0A384MTY5
ATG4C	NM_178221.3 linkuse as main transcript	c.803A>T	p.Asn268Ile	missense_variant	7/11		NP_835739.1	Q96DT6A0A384MTY5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATG4C	ENST00000317868.9 linkuse as main transcript	c.803A>T	p.Asn268Ile	missense_variant	7/11	1	NM_032852.4	ENSP00000322159.4	Q96DT6
ATG4C	ENST00000371120.7 linkuse as main transcript	c.803A>T	p.Asn268Ile	missense_variant	7/11	1		ENSP00000360161.3	Q96DT6
ATG4C	ENST00000414558.2 linkuse as main transcript	c.32A>T	p.Asn11Ile	missense_variant	2/5	5		ENSP00000391820.2	H7BZW5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 10, 2024

The c.803A>T (p.N268I) alteration is located in exon 7 (coding exon 6) of the ATG4C gene. This alteration results from a A to T substitution at nucleotide position 803, causing the asparagine (N) at amino acid position 268 to be replaced by an isoleucine (I). 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

0.097

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.043

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.52

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.086

Sift

Benign

0.37

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;B

Vest4

0.34

MutPred

0.50

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.41

MPC

0.051

ClinPred

0.40

GERP RS

1.8

Varity_R

0.089

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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