rs374994372

Positions:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_024642.5(GALNT12):c.329G>A(p.Arg110His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000066 in 1,574,710 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 1 hom. )

Consequence

GALNT12
NM_024642.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 3.52

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010430545).

BP6

Variant 9-98808027-G-A is Benign according to our data. Variant chr9-98808027-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 485648.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT12	NM_024642.5 linkuse as main transcript	c.329G>A	p.Arg110His	missense_variant	1/10	ENST00000375011.4	NP_078918.3
GALNT12	XM_006717287.1 linkuse as main transcript	c.-700G>A		5_prime_UTR_variant	1/10		XP_006717350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4 linkuse as main transcript	c.329G>A	p.Arg110His	missense_variant	1/10	1	NM_024642.5	ENSP00000364150	P1	Q8IXK2-1
GALNT12	ENST00000610463.1 linkuse as main transcript	c.26G>A	p.Arg9His	missense_variant, NMD_transcript_variant	1/4	4		ENSP00000477657

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00367

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000402

AC:

AN:

184292

Hom.:

AF XY:

0.000357

AC XY:

AN XY:

100712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00461

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000212

Gnomad NFE exome

AF:

0.0000129

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.0000576

AC:

AN:

1422544

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

704482

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00172

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000874

Gnomad4 NFE exome

AF:

9.13e-7

Gnomad4 OTH exome

AF:

0.000187

GnomAD4 genome

AF:

0.000145

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00368

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000140

ExAC

AF:

0.000339

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Aug 30, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -

Colorectal cancer, susceptibility to, 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 31, 2018

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.65

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.21

Sift

Benign

0.051

Sift4G

Uncertain

0.041

Polyphen

0.99

Vest4

0.28

MVP

0.79

MPC

0.60

ClinPred

0.17

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.60

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