GALNT12 p.Gly46Arg

Variant names:

• chr9-98807834-G-C
• rs10987768
• NM_024642.5:c.136G>C
• GALNT12 p.Gly46Arg

Your query was ambiguous. Multiple possible variants found:

• chr9-98807834-G-C
• chr9-98807834-G-A
• chr9-98807834-GGG-CGT
• chr9-98807834-GGG-CGC
• chr9-98807834-GGG-CGA
• chr9-98807834-GGG-AGA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024642.5(GALNT12):​c.136G>C​(p.Gly46Arg) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G46E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.840
• Publications: 0 publications found

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

ACMG classification

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=0.06800759).

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	NM_024642.5	MANE Select	c.136G>C	p.Gly46Arg	missense	Exon 1 of 10	NP_078918.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	ENST00000375011.4	TSL:1 MANE Select	c.136G>C	p.Gly46Arg	missense	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.136G>C	p.Gly46Arg	missense	Exon 1 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.136G>C	p.Gly46Arg	missense	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 871790 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 406524

African (AFR) AF: 0.00 AC: 0 AN: 16554

American (AMR) AF: 0.00 AC: 0 AN: 2236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6128

East Asian (EAS) AF: 0.00 AC: 0 AN: 5670

South Asian (SAS) AF: 0.00 AC: 0 AN: 17642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1790

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 788154

Other (OTH) AF: 0.00 AC: 0 AN: 29504

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.1
DANN	Benign	0.44
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.34	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.84
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.93	N
REVEL	Benign	0.071
Sift	Benign	0.25	T
Sift4G	Benign	0.41	T
PromoterAI		0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.040
gMVP		0.41
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10987768;

hg19: chr9-101570116;