Genetic Variant GALNT12:p.Arg7Pro (chr9-98807718-G-C) – 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.20G>C(p.Arg7Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7L) 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.989

Publications

0 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=0.15299764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT12	NM_024642.5 link	c.20G>C	p.Arg7Pro	missense_variant	Exon 1 of 10	ENST00000375011.4	NP_078918.3
LOC124902229	XR_007061689.1 link	n.-138C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4 link	c.20G>C	p.Arg7Pro	missense_variant	Exon 1 of 10	1	NM_024642.5	ENSP00000364150.3
ENSG00000285706	ENST00000647710.1 link	n.-154C>G		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1026360

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

494698

African (AFR)

AF:

0.00

AC:

AN:

19850

American (AMR)

AF:

0.00

AC:

AN:

7886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11388

East Asian (EAS)

AF:

0.00

AC:

AN:

15940

South Asian (SAS)

AF:

0.00

AC:

AN:

31678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15770

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2506

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

883480

Other (OTH)

AF:

0.00

AC:

AN:

37862

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 25, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.R7P variant (also known as c.20G>C), located in coding exon 1 of the GALNT12 gene, results from a G to C substitution at nucleotide position 20. The arginine at codon 7 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.016

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

0.99

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.52

REVEL

Benign

0.13

Sift

Benign

0.16

Sift4G

Benign

0.31

Polyphen

0.0010

Vest4

0.13

MutPred

0.35

Gain of glycosylation at R7 (P = 0.0123);

MVP

0.49

MPC

2.3

ClinPred

0.11

GERP RS

3.3

PromoterAI

0.0080

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.22

gMVP

0.61

Mutation Taster

=73/27

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over