ENST00000509910:c.*788G>A

Variant names:

• chr5-115831016-C-T
• rs1058600
• NM_004707.4:c.*788G>A

Variant summary

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

The ENST00000509910.2(ATG12):​c.*788G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,034 control chromosomes in the GnomAD database, including 12,590 homozygotes. 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 0.36 (12590 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ATG12 ENST00000509910.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 19 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

ENSG00000298641 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509910.2. 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.*788G>A		3_prime_UTR	Exon 4 of 4	NP_004698.3
	ATG12	NM_001277783.2		c.*849G>A		3_prime_UTR	Exon 3 of 3	NP_001264712.1	O94817-4
	ATG12	NR_033362.2		n.1341G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG12	ENST00000509910.2	TSL:1 MANE Select	c.*788G>A		3_prime_UTR	Exon 4 of 4	ENSP00000425107.1	O94817-1
	ATG12	ENST00000500945.2	TSL:1	c.*849G>A		3_prime_UTR	Exon 3 of 3	ENSP00000425164.1	O94817-4
	ATG12	ENST00000505252.1	TSL:1	n.2599G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54967 AN: 151914 Hom.: 12539 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.355

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.362 AC: 55088 AN: 152034 Hom.: 12590 Cov.: 32 AF XY: 0.361 AC XY: 26824 AN XY: 74322

African (AFR) AF: 0.634 AC: 26269 AN: 41456

American (AMR) AF: 0.434 AC: 6629 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1692 AN: 5184

South Asian (SAS) AF: 0.323 AC: 1559 AN: 4824

European-Finnish (FIN) AF: 0.167 AC: 1768 AN: 10568

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15224 AN: 67956

Other (OTH) AF: 0.354 AC: 745 AN: 2104

Alfa AF: 0.274 Hom.: 25765

Bravo AF: 0.396

Asia WGS AF: 0.338 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.32
PhyloP100		-2.5
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: rs1058600; hg19: chr5-115166713;