dbSNP rs370194003: ATG12:p.Tyr120Ser (chr5-115832606-T-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_004707.4(ATG12):c.359A>C(p.Tyr120Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000258 in 931,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000080 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ATG12
NM_004707.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.14

Publications

0 publications found

Variant links:

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

ATG12 links:

LOC124901049 (HGNC:):

LOC124901049 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.766

BS2

High AC in GnomAdExome4 at 23 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004707.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATG12	NM_004707.4	MANE Select	c.359A>C	p.Tyr120Ser	missense	Exon 3 of 4	NP_004698.3
ATG12	NM_001277783.2		c.222A>C	p.Leu74Leu	synonymous	Exon 2 of 3	NP_001264712.1	O94817-4
ATG12	NR_033362.2		n.489A>C		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATG12	ENST00000509910.2	TSL:1 MANE Select	c.359A>C	p.Tyr120Ser	missense	Exon 3 of 4	ENSP00000425107.1	O94817-1
ATG12	ENST00000500945.2	TSL:1	c.222A>C	p.Leu74Leu	synonymous	Exon 2 of 3	ENSP00000425164.1	O94817-4
ATG12	ENST00000505252.1	TSL:1	n.1747A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000799

AC:

AN:

125186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000579

AC:

AN:

172860

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000285

AC:

AN:

805942

Hom.:

Cov.:

AF XY:

0.0000361

AC XY:

AN XY:

415770

show subpopulations

African (AFR)

AF:

0.0000623

AC:

AN:

16056

American (AMR)

AF:

0.00

AC:

AN:

22636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17474

East Asian (EAS)

AF:

0.00

AC:

AN:

28092

South Asian (SAS)

AF:

0.0000340

AC:

AN:

58856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3124

European-Non Finnish (NFE)

AF:

0.0000328

AC:

AN:

578448

Other (OTH)

AF:

0.0000281

AC:

AN:

35638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000799

AC:

AN:

125186

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

58814

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32614

American (AMR)

AF:

0.00

AC:

AN:

10330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3276

East Asian (EAS)

AF:

0.00

AC:

AN:

4174

South Asian (SAS)

AF:

0.00

AC:

AN:

3884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62644

Other (OTH)

AF:

0.00

AC:

AN:

1670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000603

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.24

Eigen

Benign

0.12

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.67

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.45

PhyloP100

5.1

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-6.9

REVEL

Benign

0.29

Sift

Uncertain

0.021

Sift4G

Benign

0.081

Vest4

0.79

MVP

0.50

MPC

0.0097

ClinPred

0.86

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.69

Mutation Taster

=27/73

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over