chrX-108150266-A-G

Variant names:

• chrX-108150266-A-G
• NM_052936.5:c.929A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052936.5(ATG4A):​c.929A>G​(p.Asn310Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,098,228 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: ATG4A NM_052936.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.76

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092063874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG4A	NM_052936.5	c.929A>G	p.Asn310Ser	missense_variant	Exon 10 of 13	ENST00000372232.8	NP_443168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG4A	ENST00000372232.8	c.929A>G	p.Asn310Ser	missense_variant	Exon 10 of 13	1	NM_052936.5	ENSP00000361306.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098228 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000237

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.065	T;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.084
Sift	Benign	0.98	T;T
Sift4G	Benign	0.96	T;T
Polyphen		0.0	B;B
Vest4		0.048
MutPred		0.31		Loss of catalytic residue at N310 (P = 0.0685);.;
MVP		0.45
MPC		0.31
ClinPred		0.14	T
GERP RS		4.5
Varity_R		0.31
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-107393496;