NM_052936.5:c.299G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_052936.5(ATG4A):c.299G>A(p.Ser100Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000553 in 1,085,276 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

ATG4A
NM_052936.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.39

Publications

0 publications found

Variant links:

Genes affected

ATG4A (HGNC:16489): (autophagy related 4A 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. [provided by RefSeq, Mar 2016]

ATG4A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17070332).

BP6

Variant X-108134063-G-A is Benign according to our data. Variant chrX-108134063-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2618836.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052936.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATG4A	NM_052936.5	MANE Select	c.299G>A	p.Ser100Asn	missense	Exon 5 of 13	NP_443168.2
ATG4A	NM_178270.4		c.299G>A	p.Ser100Asn	missense	Exon 5 of 12	NP_840054.1	Q8WYN0-2
ATG4A	NM_001321287.2		c.68G>A	p.Ser23Asn	missense	Exon 6 of 14	NP_001308216.1	Q8WYN0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATG4A	ENST00000372232.8	TSL:1 MANE Select	c.299G>A	p.Ser100Asn	missense	Exon 5 of 13	ENSP00000361306.3	Q8WYN0-1
ATG4A	ENST00000345734.7	TSL:1	c.299G>A	p.Ser100Asn	missense	Exon 5 of 12	ENSP00000298131.5	Q8WYN0-2
ATG4A	ENST00000372246.7	TSL:1	n.*457G>A		non_coding_transcript_exon	Exon 6 of 14	ENSP00000361320.3	F8W7J2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000593

AC:

AN:

168492

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000553

AC:

AN:

1085276

Hom.:

Cov.:

AF XY:

0.00000564

AC XY:

AN XY:

354526

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25578

American (AMR)

AF:

0.00

AC:

AN:

31769

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18933

East Asian (EAS)

AF:

0.00

AC:

AN:

30102

South Asian (SAS)

AF:

0.00

AC:

AN:

51680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4077

European-Non Finnish (NFE)

AF:

0.00000717

AC:

AN:

837147

Other (OTH)

AF:

0.00

AC:

AN:

45590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.056

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.93

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.062

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.59

M_CAP

Benign

0.0059

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.065

PhyloP100

2.4

PrimateAI

Benign

0.38

PROVEAN

Benign

0.40

REVEL

Benign

0.039

Sift

Benign

0.20

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.078

MutPred

0.34

Loss of phosphorylation at S100 (P = 0.0324)

MVP

0.42

MPC

0.36

ClinPred

0.065

GERP RS

1.0

Varity_R

0.12

gMVP

0.19

Mutation Taster

=85/15

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over