rs1000543180

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001281504.2(ATG4D):c.-230C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000636 in 1,243,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

ATG4D
NM_001281504.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.223

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

ATG4D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27479598).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281504.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATG4D	NM_032885.6	MANE Select	c.34C>T	p.Arg12Trp	missense	Exon 1 of 10	NP_116274.3
ATG4D	NM_001281504.2		c.-230C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001268433.1
ATG4D	NM_001281504.2		c.-230C>T		5_prime_UTR	Exon 1 of 10	NP_001268433.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATG4D	ENST00000309469.9	TSL:1 MANE Select	c.34C>T	p.Arg12Trp	missense	Exon 1 of 10	ENSP00000311318.3	Q86TL0-1
ATG4D	ENST00000588667.5	TSL:1	n.34C>T		non_coding_transcript_exon	Exon 1 of 9	ENSP00000467407.1	K7EPJ0
ATG4D	ENST00000588857.5	TSL:1	n.34C>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000468290.1	K7ERK1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

AF:

0.0000706

AC:

AN:

1091070

Hom.:

Cov.:

AF XY:

0.0000796

AC XY:

AN XY:

515272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22796

American (AMR)

AF:

0.00

AC:

AN:

8304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14236

East Asian (EAS)

AF:

0.00

AC:

AN:

26380

South Asian (SAS)

AF:

0.0000513

AC:

AN:

19482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2912

European-Non Finnish (NFE)

AF:

0.0000817

AC:

AN:

918452

Other (OTH)

AF:

0.0000230

AC:

AN:

43566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.8

PhyloP100

0.22

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.34

Sift

Benign

0.045

Sift4G

Benign

0.084

Polyphen

1.0

Vest4

0.22

MutPred

0.17

Loss of MoRF binding (P = 0.0881)

MVP

0.68

MPC

0.42

ClinPred

0.93

GERP RS

3.8

PromoterAI

-0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.44

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over