NM_052936.5:c.815-49dupG

Variant names:

• chrX-108150100-T-TG
• rs3215492
• NM_052936.5:c.815-49dupG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_052936.5(ATG4A):​c.815-49dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,181,727 control chromosomes in the GnomAD database, including 87,204 homozygotes. There are 167,479 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (10710 hom., 15801 hem., cov: 0)
  • Exomes 𝑓: 0.45 (76494 hom. 151678 hem.)
• Consequence: ATG4A NM_052936.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.895
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant X-108150100-T-TG is Benign according to our data. Variant chrX-108150100-T-TG is described in ClinVar as Benign. ClinVar VariationId is 2688250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4A	NM_052936.5	MANE Select	c.815-49dupG		intron	N/A	NP_443168.2
	ATG4A	NM_178270.4		c.629-49dupG		intron	N/A	NP_840054.1	Q8WYN0-2
	ATG4A	NM_001321287.2		c.584-49dupG		intron	N/A	NP_001308216.1	Q8WYN0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4A	ENST00000372232.8	TSL:1 MANE Select	c.815-49dupG		intron	N/A	ENSP00000361306.3	Q8WYN0-1
	ATG4A	ENST00000345734.7	TSL:1	c.629-49dupG		intron	N/A	ENSP00000298131.5	Q8WYN0-2
	ATG4A	ENST00000372246.7	TSL:1	n.*973-49dupG		intron	N/A	ENSP00000361320.3	F8W7J2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 54845 AN: 110422 Hom.: 10704 Cov.: 0

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.446 AC: 477318 AN: 1071256 Hom.: 76494 Cov.: 27 AF XY: 0.443 AC XY: 151678 AN XY: 342436

African (AFR) AF: 0.679 AC: 17593 AN: 25911

American (AMR) AF: 0.195 AC: 6694 AN: 34413

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 6400 AN: 18523

East Asian (EAS) AF: 0.104 AC: 3082 AN: 29768

South Asian (SAS) AF: 0.329 AC: 16518 AN: 50157

European-Finnish (FIN) AF: 0.588 AC: 23389 AN: 39803

Middle Eastern (MID) AF: 0.377 AC: 1512 AN: 4010

European-Non Finnish (NFE) AF: 0.465 AC: 382869 AN: 823710

Other (OTH) AF: 0.428 AC: 19261 AN: 44961

GnomAD4 genome AF: 0.497 AC: 54879 AN: 110471 Hom.: 10710 Cov.: 0 AF XY: 0.482 AC XY: 15801 AN XY: 32761

African (AFR) AF: 0.678 AC: 20471 AN: 30197

American (AMR) AF: 0.261 AC: 2734 AN: 10485

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 911 AN: 2643

East Asian (EAS) AF: 0.160 AC: 567 AN: 3534

South Asian (SAS) AF: 0.300 AC: 772 AN: 2576

European-Finnish (FIN) AF: 0.584 AC: 3412 AN: 5847

Middle Eastern (MID) AF: 0.387 AC: 84 AN: 217

European-Non Finnish (NFE) AF: 0.468 AC: 24726 AN: 52779

Other (OTH) AF: 0.435 AC: 661 AN: 1518

Alfa AF: 0.509 Hom.: 3686

Bravo AF: 0.481

Asia WGS AF: 0.240 AC: 604 AN: 2505

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3215492; hg19: chrX-107393330;