GeneBe

rs751874783

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.691T>A​(p.Cys231Ser) 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. C231R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GALNT12
NM_024642.5 missense

Scores

10
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

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, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

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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, 0.923

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.691T>Ap.Cys231Ser
missense
Exon 3 of 10NP_078918.3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GALNT12
ENST00000375011.4
TSL:1 MANE Select
c.691T>Ap.Cys231Ser
missense
Exon 3 of 10ENSP00000364150.3Q8IXK2-1
GALNT12
ENST00000969913.1
c.691T>Ap.Cys231Ser
missense
Exon 3 of 11ENSP00000639972.1
GALNT12
ENST00000969912.1
c.691T>Ap.Cys231Ser
missense
Exon 3 of 11ENSP00000639971.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions
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
0.91
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.24
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.055
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Uncertain
-0.084
T
MutationAssessor
Pathogenic
3.2
M
PhyloP100
8.0
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-9.2
D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.012
D
Sift4G
Uncertain
0.0020
D
Polyphen
0.99
D
Vest4
0.95
MutPred
0.71
Gain of disorder (P = 0.2091)
MVP
0.89
MPC
0.70
ClinPred
1.0
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.93
gMVP
0.83
Mutation Taster
=13/87
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: rs751874783; hg19: chr9-101589183; API