9-98807703-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_024642.5(GALNT12):​c.5G>C​(p.Trp2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,152,366 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. W2L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:4
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11394289).
• BS2: High AC in GnomAdExome4 at 31 AD gene.

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>C	p.Trp2Ser	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.5G>C	p.Trp2Ser	missense	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.5G>C	p.Trp2Ser	missense	Exon 1 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.5G>C	p.Trp2Ser	missense	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150728 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.0000309 AC: 31 AN: 1001638 Hom.: 0 Cov.: 30 AF XY: 0.0000250 AC XY: 12 AN XY: 479476

African (AFR) AF: 0.000154 AC: 3 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: 0.000413 AC: 1 AN: 2420

European-Non Finnish (NFE) AF: 0.0000264 AC: 23 AN: 870952

Other (OTH) AF: 0.000109 AC: 4 AN: 36760

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150728 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73592

African (AFR) AF: 0.0000242 AC: 1 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: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.88
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.27	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.39	N
REVEL	Benign	0.090
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		0.0	B
Vest4		0.20
MutPred		0.35		Gain of phosphorylation at W2 (P = 0.0025)
MVP		0.24
MPC		2.5
ClinPred		0.21	T
GERP RS		-3.9
PromoterAI		0.23	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.16
gMVP		0.52
Mutation Taster		=93/7	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: rs898798901; hg19: chr9-101569985;