X-108137134-GTT-ATA

Variant names:

• chrX-108137134-GTT-ATA
• NM_052936.5:c.511_513delGTTinsATA
• ATG4A p.Val171Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_052936.5(ATG4A):​c.511_513delGTTinsATA​(p.Val171Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ATG4A NM_052936.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.02
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052936.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4A	NM_052936.5	MANE Select	c.511_513delGTTinsATA	p.Val171Ile	missense	N/A	NP_443168.2
	ATG4A	NM_178270.4		c.511_513delGTTinsATA	p.Val171Ile	missense	N/A	NP_840054.1	Q8WYN0-2
	ATG4A	NM_001321287.2		c.280_282delGTTinsATA	p.Val94Ile	missense	N/A	NP_001308216.1	Q8WYN0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG4A	ENST00000372232.8	TSL:1 MANE Select	c.511_513delGTTinsATA	p.Val171Ile	missense	N/A	ENSP00000361306.3	Q8WYN0-1
	ATG4A	ENST00000345734.7	TSL:1	c.511_513delGTTinsATA	p.Val171Ile	missense	N/A	ENSP00000298131.5	Q8WYN0-2
	ATG4A	ENST00000372246.7	TSL:1	n.*669_*671delGTTinsATA		non_coding_transcript_exon	Exon 8 of 14	ENSP00000361320.3	F8W7J2

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-107380364;