Variant 9-98831930-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_024642.5(GALNT12):c.890G>C(p.Arg297Pro) 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 pathogenic outcome for this variant. 12/21 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. R297W) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

GALNT12
NM_024642.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr9-98831929-C-T is described in Lovd as [Likely_pathogenic].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT12	NM_024642.5 linkuse as main transcript	c.890G>C	p.Arg297Pro	missense_variant	4/10	ENST00000375011.4	NP_078918.3	Q8IXK2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GALNT12	ENST00000375011.4 linkuse as main transcript	c.890G>C	p.Arg297Pro	missense_variant	4/10	1	NM_024642.5	ENSP00000364150.3	Q8IXK2-1
GALNT12	ENST00000610463.1 linkuse as main transcript	n.*321G>C		non_coding_transcript_exon_variant	3/4	4		ENSP00000477657.1	A0A087WT76
GALNT12	ENST00000610463.1 linkuse as main transcript	n.*321G>C		3_prime_UTR_variant	3/4	4		ENSP00000477657.1	A0A087WT76

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251154

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Colorectal cancer, susceptibility to, 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Jul 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.21

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.57

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.23

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0070

Polyphen

0.98

Vest4

0.62

MutPred

0.66

Loss of phosphorylation at S300 (P = 0.1024);

MVP

0.67

MPC

0.68

ClinPred

0.93

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.84

gMVP

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over