rs763057175

Variant names:

• chr9-98826890-T-A
• rs763057175
• NM_024642.5:c.680T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_024642.5(GALNT12):​c.680T>A​(p.Leu227Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,435,436 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L227V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 8.01
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.949
• BS2: High AC in GnomAdExome4 at 21 AD,Unknown 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.680T>A	p.Leu227Gln	missense	Exon 3 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.680T>A	p.Leu227Gln	missense	Exon 3 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.680T>A	p.Leu227Gln	missense	Exon 3 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.680T>A	p.Leu227Gln	missense	Exon 3 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000497 AC: 1 AN: 201190 AF XY: 0.00000925

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000146 AC: 21 AN: 1435436 Hom.: 0 Cov.: 32 AF XY: 0.0000112 AC XY: 8 AN XY: 711554

African (AFR) AF: 0.00 AC: 0 AN: 32974

American (AMR) AF: 0.00 AC: 0 AN: 40714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 38440

South Asian (SAS) AF: 0.00 AC: 0 AN: 82484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.0000191 AC: 21 AN: 1099096

Other (OTH) AF: 0.00 AC: 0 AN: 59340

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000829 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		8.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.83
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.97
MVP		0.93
MPC		0.64
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.98
gMVP		0.93
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs763057175; hg19: chr9-101589172;