rs898798901

Variant names:

• chr9-98807703-G-A
• rs898798901
• NM_024642.5:c.5G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-98807703-G-A
• chr9-98807703-G-C
• chr9-98807703-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_024642.5(GALNT12):​c.5G>A​(p.Trp2*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000521 in 1,152,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: GALNT12 NM_024642.5 stop_gained
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.30
• Publications: 2 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 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.997 CDS is truncated, and there are 2 pathogenic variants in the truncated region.

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.5G>A	p.Trp2*	stop_gained	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.5G>A	p.Trp2*	stop_gained	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.5G>A	p.Trp2*	stop_gained	Exon 1 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.5G>A	p.Trp2*	stop_gained	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150728 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome AF: 0.00000300 AC: 3 AN: 1001642 Hom.: 0 Cov.: 30 AF XY: 0.00000626 AC XY: 3 AN XY: 479478

African (AFR) AF: 0.0000514 AC: 1 AN: 19468

American (AMR) AF: 0.00 AC: 0 AN: 5998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10302

East Asian (EAS) AF: 0.00 AC: 0 AN: 15500

South Asian (SAS) AF: 0.00 AC: 0 AN: 25762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2420

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 870956

Other (OTH) AF: 0.0000272 AC: 1 AN: 36760

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150728 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73592

African (AFR) AF: 0.0000727 AC: 3 AN: 41284

American (AMR) AF: 0.00 AC: 0 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67558

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	34
DANN	Benign	0.95
Eigen	Benign	-0.034
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.37	N
PhyloP100		-1.3
Vest4		0.068
GERP RS		-3.9
PromoterAI		0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=8/192	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs898798901; hg19: chr9-101569985;