X-108153135-G-A

Variant names:

• chrX-108153135-G-A
• rs1883411
• NM_052936.5:c.1126+48G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052936.5(ATG4A):​c.1126+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 906,757 control chromosomes in the GnomAD database, including 71,456 homozygotes. There are 115,420 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (10721 hom., 15884 hem., cov: 23)
  • Exomes 𝑓: 0.45 (60735 hom. 99536 hem.)
• Consequence: ATG4A NM_052936.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.441

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-108153135-G-A is Benign according to our data. Variant chrX-108153135-G-A is described in ClinVar as [Benign]. Clinvar id is 2688198.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG4A	NM_052936.5	c.1126+48G>A		intron_variant	Intron 12 of 12	ENST00000372232.8	NP_443168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4A	ENST00000372232.8	c.1126+48G>A		intron_variant	Intron 12 of 12	1	NM_052936.5	ENSP00000361306.3

Frequencies

GnomAD3 genomes AF: 0.498 AC: 54933 AN: 110365 Hom.: 10713 Cov.: 23

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.430

GnomAD2 exomes AF: 0.414 AC: 62245 AN: 150306 AF XY: 0.417

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.173

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.449 AC: 357206 AN: 796335 Hom.: 60735 Cov.: 12 AF XY: 0.468 AC XY: 99536 AN XY: 212861

Gnomad4 AFR exome AF: 0.686 AC: 14164 AN: 20661

Gnomad4 AMR exome AF: 0.200 AC: 6399 AN: 32066

Gnomad4 ASJ exome AF: 0.349 AC: 5987 AN: 17159

Gnomad4 EAS exome AF: 0.101 AC: 2853 AN: 28135

Gnomad4 SAS exome AF: 0.333 AC: 14974 AN: 44957

Gnomad4 FIN exome AF: 0.590 AC: 23336 AN: 39527

Gnomad4 NFE exome AF: 0.474 AC: 272488 AN: 574326

Gnomad4 Remaining exome AF: 0.435 AC: 15670 AN: 36004

GnomAD4 genome AF: 0.498 AC: 54983 AN: 110422 Hom.: 10721 Cov.: 23 AF XY: 0.486 AC XY: 15884 AN XY: 32708

Gnomad4 AFR AF: 0.680 AC: 0.679958 AN: 0.679958

Gnomad4 AMR AF: 0.264 AC: 0.264147 AN: 0.264147

Gnomad4 ASJ AF: 0.346 AC: 0.346358 AN: 0.346358

Gnomad4 EAS AF: 0.160 AC: 0.16008 AN: 0.16008

Gnomad4 SAS AF: 0.295 AC: 0.294931 AN: 0.294931

Gnomad4 FIN AF: 0.591 AC: 0.590886 AN: 0.590886

Gnomad4 NFE AF: 0.468 AC: 0.467885 AN: 0.467885

Gnomad4 OTH AF: 0.434 AC: 0.434202 AN: 0.434202

Alfa AF: 0.463 Hom.: 46749

Bravo AF: 0.481

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 37% of patients studied by a panel of primary immunodeficiencies. Number of patients: 35. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.51
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: rs1883411; hg19: chrX-107396365; COSMIC: COSV57864730; COSMIC: COSV57864730;