rs41306504

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024642.5(GALNT12):c.781G>A(p.Asp261Asn) variant causes a missense change. The variant allele was found at a frequency of 0.012 in 1,614,166 control chromosomes in the GnomAD database, including 164 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. D261H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.010 ( 12 hom., cov: 32)

Exomes 𝑓: 0.012 ( 152 hom. )

Consequence

GALNT12
NM_024642.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 6.84

Publications

12 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010009915).

BP6

Variant 9-98831821-G-A is Benign according to our data. Variant chr9-98831821-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0122 (17892/1461884) while in subpopulation MID AF = 0.0194 (112/5768). AF 95% confidence interval is 0.0165. There are 152 homozygotes in GnomAdExome4. There are 9125 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1547 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT12	NM_024642.5 link	c.781G>A	p.Asp261Asn	missense_variant	Exon 4 of 10	ENST00000375011.4	NP_078918.3	Q8IXK2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT12	ENST00000375011.4 link	c.781G>A	p.Asp261Asn	missense_variant	Exon 4 of 10	1	NM_024642.5	ENSP00000364150.3	Q8IXK2-1
GALNT12	ENST00000610463.1 link	n.*212G>A		non_coding_transcript_exon_variant	Exon 3 of 4	4		ENSP00000477657.1	A0A087WT76
GALNT12	ENST00000610463.1 link	n.*212G>A		3_prime_UTR_variant	Exon 3 of 4	4		ENSP00000477657.1	A0A087WT76

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1546

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.0119

AC:

2988

AN:

251464

AF XY:

0.0125

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00925

Gnomad ASJ exome

AF:

0.00694

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0250

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0122

AC:

17892

AN:

1461884

Hom.:

152

Cov.:

AF XY:

0.0125

AC XY:

9125

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00227

AC:

AN:

33480

American (AMR)

AF:

0.00953

AC:

426

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00704

AC:

184

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39698

South Asian (SAS)

AF:

0.0159

AC:

1373

AN:

86252

European-Finnish (FIN)

AF:

0.0233

AC:

1247

AN:

53420

Middle Eastern (MID)

AF:

0.0194

AC:

112

AN:

5768

European-Non Finnish (NFE)

AF:

0.0123

AC:

13723

AN:

1112010

Other (OTH)

AF:

0.0123

AC:

744

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1046

2092

3139

4185

5231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.0102

AC:

1547

AN:

152282

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

769

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00272

AC:

113

AN:

41554

American (AMR)

AF:

0.0101

AC:

154

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0250

AC:

265

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

878

AN:

68018

Other (OTH)

AF:

0.0175

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

156

234

312

390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0108

Hom.:

Bravo

AF:

0.00858

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0114

AC:

ExAC

AF:

0.0114

AC:

1385

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0146

EpiControl

AF:

0.0143

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 23, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Aug 26, 2016

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. -

Apr 19, 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

Sep 09, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Jan 10, 2025

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The missense variant NM_024642.5(GALNT12):c.781G>A (p.Asp261Asn) has been reported to ClinVar as Benign/Likely benign with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 241517 as of 2025-01-02). There is a small physicochemical difference between aspartic acid and asparagine, which is not likely to impact secondary protein structure as these residues share similar properties. For these reasons, this variant has been classified as Benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.2

PhyloP100

6.8

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.34

Sift

Benign

0.060

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.25

MPC

0.60

ClinPred

0.0091

GERP RS

5.7

Varity_R

0.70

gMVP

0.71

Mutation Taster

=83/17

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over