Genetic Variant NM_024642.5:c.25C>A (chr9-98807723-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024642.5(GALNT12):c.25C>A(p.Arg9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GALNT12
NM_024642.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.55

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13834393).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024642.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	NM_024642.5	MANE Select	c.25C>A	p.Arg9Ser	missense	Exon 1 of 10	NP_078918.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	ENST00000375011.4	TSL:1 MANE Select	c.25C>A	p.Arg9Ser	missense	Exon 1 of 10	ENSP00000364150.3
	ENSG00000285706	ENST00000647710.1		n.-159G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1029612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

496710

African (AFR)

AF:

0.00

AC:

AN:

19878

American (AMR)

AF:

0.00

AC:

AN:

8266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11584

East Asian (EAS)

AF:

0.00

AC:

AN:

15866

South Asian (SAS)

AF:

0.00

AC:

AN:

32778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2512

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

884800

Other (OTH)

AF:

0.00

AC:

AN:

37972

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.013

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.010

REVEL

Benign

0.053

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.054

Polyphen

0.078

Vest4

0.27

MutPred

0.29

Gain of phosphorylation at R9 (P = 0.0039)

MVP

0.40

MPC

2.0

ClinPred

0.23

GERP RS

1.4

PromoterAI

-0.0089

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.15

gMVP

0.57

Mutation Taster

=91/9

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over