rs41306504

Positions:

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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:6

Conservation

PhyloP100: 6.84

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 Benign. Variant got -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 [Likely_benign]. Clinvar id is 241517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-98831821-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 9125 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1547 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT12	NM_024642.5 linkuse as main transcript	c.781G>A	p.Asp261Asn	missense_variant	4/10	ENST00000375011.4	NP_078918.3	Q8IXK2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GALNT12	ENST00000375011.4 linkuse as main transcript	c.781G>A	p.Asp261Asn	missense_variant	4/10	1	NM_024642.5	ENSP00000364150.3	Q8IXK2-1
GALNT12	ENST00000610463.1 linkuse as main transcript	n.*212G>A		non_coding_transcript_exon_variant	3/4	4		ENSP00000477657.1	A0A087WT76
GALNT12	ENST00000610463.1 linkuse as main transcript	n.*212G>A		3_prime_UTR_variant	3/4	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

GnomAD3 exomes

AF:

0.0119

AC:

2988

AN:

251464

Hom.:

AF XY:

0.0125

AC XY:

1703

AN XY:

135902

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 SAS exome

AF:

0.0147

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

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.00953

Gnomad4 ASJ exome

AF:

0.00704

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0159

Gnomad4 FIN exome

AF:

0.0233

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.0102

AC:

1547

AN:

152282

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

769

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0111

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, 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	GeneDx	Feb 23, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 26, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Apr 19, 2021	- -

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

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

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

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

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