9-98807692-CGGGCGCATGTGG-CGGGCGCATGTGGGGGCGCATGTGG

Variant names:

• chr9-98807692-C-CGGGCGCATGTGG
• rs1835403535
• NM_024642.5:c.2_13dupTGTGGGGGCGCA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_024642.5(GALNT12):​c.2_13dupTGTGGGGGCGCA​(p.Met1_Arg4dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 983,984 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T5T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: GALNT12 NM_024642.5 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.132
• 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: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ENSG00000285706 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_024642.5.

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.2_13dupTGTGGGGGCGCA	p.Met1_Arg4dup	disruptive_inframe_insertion	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.2_13dupTGTGGGGGCGCA	p.Met1_Arg4dup	disruptive_inframe_insertion	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.2_13dupTGTGGGGGCGCA	p.Met1_Arg4dup	disruptive_inframe_insertion	Exon 1 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.2_13dupTGTGGGGGCGCA	p.Met1_Arg4dup	disruptive_inframe_insertion	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 983984 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 468798

African (AFR) AF: 0.00 AC: 0 AN: 19094

American (AMR) AF: 0.00 AC: 0 AN: 4948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9544

East Asian (EAS) AF: 0.0000675 AC: 1 AN: 14822

South Asian (SAS) AF: 0.00 AC: 0 AN: 23392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2346

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 860698

Other (OTH) AF: 0.00 AC: 0 AN: 35866

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs1835403535; hg19: chr9-101569974;