9-98840128-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024642.5(GALNT12):​c.1339G>C​(p.Gly447Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

GALNT12
NM_024642.5 missense

Scores

11
6
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GALNT12NM_024642.5 linkc.1339G>C p.Gly447Arg missense_variant Exon 7 of 10 ENST00000375011.4 NP_078918.3 Q8IXK2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GALNT12ENST00000375011.4 linkc.1339G>C p.Gly447Arg missense_variant Exon 7 of 10 1 NM_024642.5 ENSP00000364150.3 Q8IXK2-1
GALNT12ENST00000615204.1 linkn.201G>C non_coding_transcript_exon_variant Exon 2 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461064
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726834
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.34
T
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.89
D
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Pathogenic
3.4
M
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-5.9
D
REVEL
Uncertain
0.63
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.98
MutPred
0.66
Loss of ubiquitination at K452 (P = 0.0464);
MVP
0.70
MPC
0.69
ClinPred
1.0
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.98
gMVP
0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-101602410; API