rs878855093

Variant names:

• chr9-98807834-GGG-AGA
• rs878855093
• NM_024642.5:c.136_138delGGGinsAGA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_024642.5(GALNT12):​c.136_138delGGGinsAGA​(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. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.000279 in 7 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). 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: GnomAD MNV: 𝑓 0.00028 Genomes: not found (cov: 32)
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:4
• Conservation: PhyloP100: -0.0180
• Publications: 3 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: AD Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 9-98807834-GGG-AGA is Benign according to our data. Variant chr9-98807834-GGG-AGA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 241508.
• BS2: High AC in GnomAdMnv at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT12	NM_024642.5	c.136_138delGGGinsAGA	p.Gly46Arg	missense_variant		ENST00000375011.4	NP_078918.3
GALNT12	XM_006717287.1	c.-893_-891delGGGinsAGA		upstream_gene_variant			XP_006717350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4	c.136_138delGGGinsAGA	p.Gly46Arg	missense_variant		1	NM_024642.5	ENSP00000364150.3
GALNT12	ENST00000610463.1	n.-171_-169delGGGinsAGA		upstream_gene_variant		4		ENSP00000477657.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

GnomAD MNV AF: 0.000279 AC: 7 Hom.: 0

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:4

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Benign:2

Sep 14, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Dec 25, 2015

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Colorectal cancer, susceptibility to, 1 Uncertain:1

Jun 24, 2022

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Oct 25, 2022

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GALNT12-related disorder Benign:1

Aug 01, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.018

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs878855093; hg19: chr9-101570116;