9-98807699-A-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PVS1_ModerateBS2

The NM_024642.5(GALNT12):c.1A>C(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,145,792 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

GALNT12
NM_024642.5 initiator_codon

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 0.464

Publications

1 publications found

Variant links:

Genes affected

GALNT12 (HGNC:19877): (polypeptide N-acetylgalactosaminyltransferase 12) This gene encodes a member of a family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases, which catalyze the transfer of N-acetylgalactosamine (GalNAc) from UDP-GalNAc to a serine or threonine residue on a polypeptide acceptor in the initial step of O-linked protein glycosylation. Mutations in this gene are associated with an increased susceptibility to colorectal cancer.[provided by RefSeq, Mar 2011]

GALNT12 Gene-Disease associations (from GenCC):

colorectal cancer, susceptibility to, 1
Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

GALNT12 links:

ENSG00000285706 (HGNC:):

ENSG00000285706 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 2 pathogenic variants. Next in-frame start position is after 65 codons. Genomic position: 98807891. Lost 0.111 part of the original CDS.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT12	NM_024642.5 link	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 10	ENST00000375011.4	NP_078918.3	Q8IXK2-1
LOC124902229	XR_007061689.1 link	n.-119T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4 link	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 10	1	NM_024642.5	ENSP00000364150.3		Q8IXK2-1
ENSG00000285706	ENST00000647710.1 link	n.-135T>G		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

995228

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

475612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19344

American (AMR)

AF:

0.00

AC:

AN:

5592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9992

East Asian (EAS)

AF:

0.00

AC:

AN:

15214

South Asian (SAS)

AF:

0.00

AC:

AN:

25148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2384

European-Non Finnish (NFE)

AF:

0.0000115

AC:

AN:

867044

Other (OTH)

AF:

0.00

AC:

AN:

36408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150564

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73510

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41164

American (AMR)

AF:

0.00

AC:

AN:

15140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67562

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 29, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant has not been reported in the literature in individuals with GALNT12-related conditions. ClinVar contains an entry for this variant (Variation ID: 820494). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that disruption of the initiator codon affects GALNT12 protein function (PMID: 19617566). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change affects the initiator methionine of the GALNT12 mRNA. The next in-frame methionine is located at codon 65. -

not specified

Uncertain:1

Nov 22, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.M1? variant (also known as c.1A>C) is located in coding exon 1 of the GALNT12 gene and results from an A to C substitution at nucleotide position 1.This alters the methionine residue at the initiation codon (ATG). The c.1A>C alteration is expected to modify the initiation codon (ATG) resulting in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. -

Colorectal cancer, susceptibility to, 1

Uncertain:1

Mar 28, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.012

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.97

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-1.0

PhyloP100

0.46

PROVEAN

Benign

-0.070

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.055

Vest4

0.78

MutPred

0.61

Loss of loop (P = 0.1258);

MVP

0.32

ClinPred

0.97

GERP RS

3.3

PromoterAI

0.046

Neutral

(source)

Varity_R

0.90

gMVP

0.49

Mutation Taster

=18/182

disease causing

(source)

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

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.

9-98807699-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over