rs5973822

Variant names:

• chrX-108153728-A-G
• rs5973822
• ENST00000372246.7:n.*1371A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000372246.7(ATG4A):​n.*1371A>G variant causes a non coding transcript exon 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 ENST00000372246.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 12 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 -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 rank	MANE	Protein	UniProt
ATG4A	NM_052936.5	c.*16A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000372232.8	NP_443168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4A	ENST00000372232.8	c.*16A>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_052936.5	ENSP00000361306.3

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 5700 AN: 111775 Hom.: 127 Cov.: 23

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

GnomAD2 exomes AF: 0.0512 AC: 9058 AN: 177040 AF XY: 0.0503

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 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

African (AFR) AF: 0.0562 AC: 1448 AN: 25781

American (AMR) AF: 0.0458 AC: 1578 AN: 34480

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 749 AN: 19083

East Asian (EAS) AF: 0.0699 AC: 2099 AN: 30020

South Asian (SAS) AF: 0.0396 AC: 2063 AN: 52073

European-Finnish (FIN) AF: 0.0380 AC: 1537 AN: 40436

Middle Eastern (MID) AF: 0.0623 AC: 253 AN: 4061

European-Non Finnish (NFE) AF: 0.0456 AC: 37306 AN: 817600

Other (OTH) AF: 0.0500 AC: 2259 AN: 45140

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

African (AFR) AF: 0.0575 AC: 1766 AN: 30717

American (AMR) AF: 0.0371 AC: 392 AN: 10553

Ashkenazi Jewish (ASJ) AF: 0.0382 AC: 101 AN: 2641

East Asian (EAS) AF: 0.0979 AC: 348 AN: 3555

South Asian (SAS) AF: 0.0342 AC: 92 AN: 2687

European-Finnish (FIN) AF: 0.0341 AC: 207 AN: 6062

Middle Eastern (MID) AF: 0.0599 AC: 13 AN: 217

European-Non Finnish (NFE) AF: 0.0489 AC: 2601 AN: 53199

Other (OTH) AF: 0.0361 AC: 55 AN: 1525

Alfa AF: 0.0478 Hom.: 2187

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
PhyloP100		-0.14
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: rs5973822; hg19: chrX-107396958;