9-98808057-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024642.5(GALNT12):c.359G>C(p.Arg120Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,578,224 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

GALNT12
NM_024642.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.17

Publications

4 publications found

Variant links:

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 Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

GALNT12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01616779).

BP6

Variant 9-98808057-G-C is Benign according to our data. Variant chr9-98808057-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 67 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	NM_024642.5	MANE Select	c.359G>C	p.Arg120Pro	missense	Exon 1 of 10	NP_078918.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	ENST00000375011.4	TSL:1 MANE Select	c.359G>C	p.Arg120Pro	missense	Exon 1 of 10	ENSP00000364150.3
	GALNT12	ENST00000610463.1	TSL:4	n.53G>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000477657.1

Frequencies

GnomAD3 genomes

AF:

0.000441

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000659

AC:

123

AN:

186706

AF XY:

0.000676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000685

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.000413

GnomAD4 exome

AF:

0.000296

AC:

422

AN:

1426130

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

222

AN XY:

706548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33046

American (AMR)

AF:

0.0000494

AC:

AN:

40496

Ashkenazi Jewish (ASJ)

AF:

0.0125

AC:

317

AN:

25430

East Asian (EAS)

AF:

0.00

AC:

AN:

38540

South Asian (SAS)

AF:

0.00

AC:

AN:

81536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4656

European-Non Finnish (NFE)

AF:

0.0000501

AC:

AN:

1097380

Other (OTH)

AF:

0.000812

AC:

AN:

59092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000441

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.000412

ExAC

AF:

0.000382

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 08, 2019

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Jun 23, 2021

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Colorectal cancer, susceptibility to, 1

Benign:1

Jan 09, 2025

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Dec 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hereditary cancer-predisposing syndrome

Benign:1

Jan 15, 2025

Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The missense variant NM_024642.5(GALNT12):c.359G>C (p.Arg120Pro) has been reported to ClinVar as Benign with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 241512 as of 2025-01-02). There is a moderate physicochemical difference between arginine and proline. The nucleotide c.359 in GALNT12 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Benign.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0095

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.76

PhyloP100

3.2

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.51

REVEL

Benign

0.19

Sift

Benign

0.51

Sift4G

Benign

0.31

Polyphen

1.0

Vest4

0.55

MVP

0.73

MPC

0.64

ClinPred

0.063

GERP RS

3.7

PromoterAI

0.059

Neutral

(source)

Varity_R

0.77

gMVP

0.82

Mutation Taster

=53/47

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over