rs145236923

Positions:

chr9-98831947-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024642.5(GALNT12):c.907G>A(p.Asp303Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,613,758 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 7 hom. )

Consequence

GALNT12
NM_024642.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:5

Conservation

PhyloP100: 9.92

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.093777746).

BS2

High AC in GnomAd4 at 187 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT12	NM_024642.5 linkuse as main transcript	c.907G>A	p.Asp303Asn	missense_variant	4/10	ENST00000375011.4	NP_078918.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4 linkuse as main transcript	c.907G>A	p.Asp303Asn	missense_variant	4/10	1	NM_024642.5	ENSP00000364150	P1	Q8IXK2-1
GALNT12	ENST00000610463.1 linkuse as main transcript	c.*338G>A		3_prime_UTR_variant, NMD_transcript_variant	3/4	4		ENSP00000477657

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00124

AC:

312

AN:

250702

Hom.:

AF XY:

0.00130

AC XY:

176

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.000956

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00188

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00189

AC:

2766

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1350

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00210

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.00123

AC:

187

AN:

152268

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00191

Hom.:

Bravo

AF:

0.00132

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00114

AC:

138

EpiCase

AF:

0.00196

EpiControl

AF:

0.00249

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Uncertain significance, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Oct 07, 2022	- -

Hereditary cancer-predisposing syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

University of Washington Department of Laboratory Medicine, University of Washington

Nov 20, 2015

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2020

This alteration is classified as likely 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. -

Adenomatous polyposis coli, attenuated

Benign:1

Benign, no assertion criteria provided

research

Molecular Oncology Laboratory, Hospital Clínico San Carlos

No statistical differences in allelic frequencies between polyposis subjects and controls. No aberrant glycosylation patterns detected in adenomas of polyposis cases. -

GALNT12-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 14, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.062

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.40

Sift

Benign

0.050

Sift4G

Benign

0.088

Polyphen

1.0

Vest4

0.77

MVP

0.82

MPC

0.62

ClinPred

0.047

GERP RS

5.7

Varity_R

0.60

gMVP

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over