9-98807718-G-A

Variant names:

• chr9-98807718-G-A
• rs568625965
• NM_024642.5:c.20G>A

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.20G>A​(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,026,358 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R7L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.989
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1783219).

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.20G>A	p.Arg7Gln	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.20G>A	p.Arg7Gln	missense	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.20G>A	p.Arg7Gln	missense	Exon 1 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.20G>A	p.Arg7Gln	missense	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150328 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00000195 AC: 2 AN: 1026358 Hom.: 0 Cov.: 30 AF XY: 0.00000202 AC XY: 1 AN XY: 494698

African (AFR) AF: 0.0000504 AC: 1 AN: 19850

American (AMR) AF: 0.00 AC: 0 AN: 7886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11388

East Asian (EAS) AF: 0.00 AC: 0 AN: 15940

South Asian (SAS) AF: 0.0000316 AC: 1 AN: 31678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2506

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 883480

Other (OTH) AF: 0.00 AC: 0 AN: 37860

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150328 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73364

African (AFR) AF: 0.00 AC: 0 AN: 41260

American (AMR) AF: 0.00 AC: 0 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9882

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67370

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.99
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.29	N
REVEL	Benign	0.10
Sift	Benign	0.36	T
Sift4G	Benign	0.36	T
Polyphen		0.91	P
Vest4		0.081
MutPred		0.39		Loss of phosphorylation at T5 (P = 0.0901)
MVP		0.56
MPC		2.0
ClinPred		0.23	T
GERP RS		3.3
PromoterAI		-0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.10
gMVP		0.46
Mutation Taster		=96/4	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

Other links and lift over

dbSNP: rs568625965; hg19: chr9-101570000;