rs1472145598

Variant names:

• chr9-98840066-AGTGGTTCTTGGAGACT-A
• rs1472145598
• NM_024642.5:c.1281_1296delGTTCTTGGAGACTGTG

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_024642.5(GALNT12):​c.1281_1296delGTTCTTGGAGACTGTG​(p.Trp427CysfsTer23) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 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 DEL_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 (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: GALNT12 NM_024642.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:5
• Conservation: PhyloP100: 10.0
• Publications: 1 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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

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.1281_1296delGTTCTTGGAGACTGTG	p.Trp427CysfsTer23	frameshift	Exon 7 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.1281_1296delGTTCTTGGAGACTGTG	p.Trp427CysfsTer23	frameshift	Exon 7 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.1401_1416delGTTCTTGGAGACTGTG	p.Trp467CysfsTer23	frameshift	Exon 8 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.1281_1296delGTTCTTGGAGACTGTG	p.Trp427CysfsTer38	frameshift	Exon 7 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	1	-	Colorectal cancer (1)
-	1	-	Colorectal cancer, susceptibility to, 1 (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10
Mutation Taster		=2/198	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs1472145598; hg19: chr9-101602348;