Genetic Variant GALNT12:p.Trp2* (chr9-98807704-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_024642.5(GALNT12):c.6G>A(p.Trp2*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GALNT12
NM_024642.5 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

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_pathogenic. The variant received 6 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.997 CDS is truncated, and there are 2 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT12	NM_024642.5 link	c.6G>A	p.Trp2*	stop_gained	Exon 1 of 10	ENST00000375011.4	NP_078918.3	Q8IXK2-1
LOC124902229	XR_007061689.1 link	n.-124C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4 link	c.6G>A	p.Trp2*	stop_gained	Exon 1 of 10	1	NM_024642.5	ENSP00000364150.3		Q8IXK2-1
ENSG00000285706	ENST00000647710.1 link	n.-140C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150742

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1003116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

480448

African (AFR)

AF:

0.00

AC:

AN:

19496

American (AMR)

AF:

0.00

AC:

AN:

6102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10346

East Asian (EAS)

AF:

0.00

AC:

AN:

15538

South Asian (SAS)

AF:

0.00

AC:

AN:

26054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2422

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

871770

Other (OTH)

AF:

0.00

AC:

AN:

36832

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150742

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73604

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41282

American (AMR)

AF:

0.00

AC:

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67572

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000843

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.20

PhyloP100

1.2

Vest4

0.068

GERP RS

2.4

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=9/191

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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9-98807704-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over