rs5973822

Positions:

• chrX-108153728-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052936.5(ATG4A):​c.*16A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,180,502 control chromosomes in the GnomAD database, including 994 homozygotes. There are 17,240 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (127 hom., 1629 hem., cov: 23)
  • Exomes 𝑓: 0.046 (867 hom. 15611 hem.)
• Consequence: ATG4A NM_052936.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG4A	NM_052936.5	c.*16A>G		3_prime_UTR_variant	13/13	ENST00000372232.8	NP_443168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG4A	ENST00000372232.8	c.*16A>G		3_prime_UTR_variant	13/13	1	NM_052936.5	ENSP00000361306	P1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 5700 AN: 111775 Hom.: 127 Cov.: 23 AF XY: 0.0478 AC XY: 1622 AN XY: 33957

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0372

Gnomad ASJ AF: 0.0382

Gnomad EAS AF: 0.0979

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0546

Gnomad NFE AF: 0.0489

Gnomad OTH AF: 0.0352

GnomAD3 exomes AF: 0.0512 AC: 9058 AN: 177040 Hom.: 173 AF XY: 0.0503 AC XY: 3114 AN XY: 61940

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.0460

Gnomad ASJ exome AF: 0.0394

Gnomad EAS exome AF: 0.0993

Gnomad SAS exome AF: 0.0402

Gnomad FIN exome AF: 0.0362

Gnomad NFE exome AF: 0.0495

Gnomad OTH exome AF: 0.0520

GnomAD4 exome AF: 0.0461 AC: 49292 AN: 1068674 Hom.: 867 Cov.: 24 AF XY: 0.0464 AC XY: 15611 AN XY: 336702

Gnomad4 AFR exome AF: 0.0562

Gnomad4 AMR exome AF: 0.0458

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.0699

Gnomad4 SAS exome AF: 0.0396

Gnomad4 FIN exome AF: 0.0380

Gnomad4 NFE exome AF: 0.0456

Gnomad4 OTH exome AF: 0.0500

GnomAD4 genome AF: 0.0511 AC: 5710 AN: 111828 Hom.: 127 Cov.: 23 AF XY: 0.0479 AC XY: 1629 AN XY: 34020

Gnomad4 AFR AF: 0.0575

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0382

Gnomad4 EAS AF: 0.0979

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0489

Gnomad4 OTH AF: 0.0361

Alfa AF: 0.0480 Hom.: 1769

Bravo AF: 0.0519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.7
DANN	Benign	0.81

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: rs5973822; hg19: chrX-107396958;