5-115832605-AT-GC

Variant names:

• chr5-115832605-AT-GC
• ENST00000500945.2:c.222_223delATinsGC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001277783.2(ATG12):​c.222_223delATinsGC​(p.Ter75Argext*?) variant causes a stop lost change. 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. Synonymous variant affecting the same amino acid position (i.e. L74L) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 25)
• Consequence: ATG12 NM_001277783.2 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17
• Publications: 0 publications found

Genes affected

ATG12 (HGNC:588): (autophagy related 12) Autophagy is a process of bulk protein degradation in which cytoplasmic components, including organelles, are enclosed in double-membrane structures called autophagosomes and delivered to lysosomes or vacuoles for degradation. ATG12 is the human homolog of a yeast protein involved in autophagy (Mizushima et al., 1998 [PubMed 9852036]).[supplied by OMIM, Mar 2008]

ATG12 Gene-Disease associations (from GenCC):

• colorectal cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC124901049 (HGNC:):

ENSG00000298641 (HGNC:59117):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Stoplost variant in NM_001277783.2 Downstream stopcodon found after 1222 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277783.2. 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
	ATG12	NM_004707.4	MANE Select	c.359_360delATinsGC	p.Tyr120Cys	missense	N/A	NP_004698.3
	ATG12	NM_001277783.2		c.222_223delATinsGC	p.Ter75Argext*?	stop_lost	N/A	NP_001264712.1	O94817-4
	ATG12	NR_033362.2		n.489_490delATinsGC		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG12	ENST00000500945.2	TSL:1	c.222_223delATinsGC	p.Ter75Argext*?	stop_lost	N/A	ENSP00000425164.1	O94817-4
	ATG12	ENST00000509910.2	TSL:1 MANE Select	c.359_360delATinsGC	p.Tyr120Cys	missense	N/A	ENSP00000425107.1	O94817-1
	ATG12	ENST00000505252.1	TSL:1	n.1747_1748delATinsGC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 25

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

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

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: chr5-115168302;