X-108150100-T-TG

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

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG4A	NM_052936.5	c.815-49dupG		intron_variant	Intron 9 of 12	ENST00000372232.8	NP_443168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4A	ENST00000372232.8	c.815-49dupG		intron_variant	Intron 9 of 12	1	NM_052936.5	ENSP00000361306.3

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

Gnomad4 AFR exome AF: 0.679 AC: 17593 AN: 25911

Gnomad4 AMR exome AF: 0.195 AC: 6694 AN: 34413

Gnomad4 ASJ exome AF: 0.346 AC: 6400 AN: 18523

Gnomad4 EAS exome AF: 0.104 AC: 3082 AN: 29768

Gnomad4 SAS exome AF: 0.329 AC: 16518 AN: 50157

Gnomad4 FIN exome AF: 0.588 AC: 23389 AN: 39803

Gnomad4 NFE exome AF: 0.465 AC: 382869 AN: 823710

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.678 AC: 0.677915 AN: 0.677915

Gnomad4 AMR AF: 0.261 AC: 0.260753 AN: 0.260753

Gnomad4 ASJ AF: 0.345 AC: 0.344684 AN: 0.344684

Gnomad4 EAS AF: 0.160 AC: 0.160441 AN: 0.160441

Gnomad4 SAS AF: 0.300 AC: 0.299689 AN: 0.299689

Gnomad4 FIN AF: 0.584 AC: 0.583547 AN: 0.583547

Gnomad4 NFE AF: 0.468 AC: 0.468482 AN: 0.468482

Gnomad4 OTH AF: 0.435 AC: 0.435441 AN: 0.435441

Alfa AF: 0.509 Hom.: 3686

Bravo AF: 0.481

Asia WGS AF: 0.240 AC: 604 AN: 2505

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs3215492; hg19: chrX-107393330;