GeneBe

rs267606840

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024642.5(GALNT12):​c.1472C>A​(p.Thr491Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T491M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GALNT12
NM_024642.5 missense

Scores

7
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.33

Publications

6 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)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.866

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GALNT12
NM_024642.5
MANE Select
c.1472C>Ap.Thr491Lys
missense
Exon 9 of 10NP_078918.3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GALNT12
ENST00000375011.4
TSL:1 MANE Select
c.1472C>Ap.Thr491Lys
missense
Exon 9 of 10ENSP00000364150.3
GALNT12
ENST00000969913.1
c.1592C>Ap.Thr531Lys
missense
Exon 10 of 11ENSP00000639972.1
GALNT12
ENST00000969912.1
c.1517C>Ap.Thr506Lys
missense
Exon 10 of 11ENSP00000639971.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.76
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.055
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Benign
-0.54
T
MutationAssessor
Pathogenic
3.3
M
PhyloP100
7.3
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-3.8
D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.91
P
Vest4
0.72
MutPred
0.71
Gain of ubiquitination at T491 (P = 0.0289)
MVP
0.75
MPC
0.67
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.97
gMVP
0.83
Mutation Taster
=29/71
disease causing

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

Other links and lift over

dbSNP: rs267606840; hg19: chr9-101608272; API