chr9-98807834-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024642.5(GALNT12):c.136G>A(p.Gly46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,018,778 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G46E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.034 ( 267 hom., cov: 32)

Exomes 𝑓: 0.019 ( 418 hom. )

Consequence

GALNT12
NM_024642.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.840

Publications

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

GALNT12 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_024642.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016487539).

BP6

Variant 9-98807834-G-A is Benign according to our data. Variant chr9-98807834-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 485632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	NM_024642.5	MANE Select	c.136G>A	p.Gly46Arg	missense	Exon 1 of 10	NP_078918.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GALNT12	ENST00000375011.4	TSL:1 MANE Select	c.136G>A	p.Gly46Arg	missense	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
GALNT12	ENST00000969913.1		c.136G>A	p.Gly46Arg	missense	Exon 1 of 11	ENSP00000639972.1
GALNT12	ENST00000969912.1		c.136G>A	p.Gly46Arg	missense	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5054

AN:

146900

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0803

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0918

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0347

GnomAD2 exomes

AF:

0.0192

AC:

AN:

AF XY:

0.00

show subpopulations

Gnomad NFE exome

AF:

0.0227

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0186

AC:

16223

AN:

871770

Hom.:

418

Cov.:

AF XY:

0.0185

AC XY:

7539

AN XY:

406522

show subpopulations

African (AFR)

AF:

0.00266

AC:

AN:

16554

American (AMR)

AF:

0.132

AC:

295

AN:

2236

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

6128

East Asian (EAS)

AF:

0.219

AC:

1240

AN:

5668

South Asian (SAS)

AF:

0.0776

AC:

1368

AN:

17640

European-Finnish (FIN)

AF:

0.124

AC:

508

AN:

4108

Middle Eastern (MID)

AF:

0.00950

AC:

AN:

1790

European-Non Finnish (NFE)

AF:

0.0149

AC:

11723

AN:

788144

Other (OTH)

AF:

0.0323

AC:

954

AN:

29502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

928

1856

2783

3711

4639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.0344

AC:

5058

AN:

147008

Hom.:

267

Cov.:

AF XY:

0.0415

AC XY:

2972

AN XY:

71570

show subpopulations

African (AFR)

AF:

0.00492

AC:

202

AN:

41040

American (AMR)

AF:

0.0810

AC:

1197

AN:

14784

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3392

East Asian (EAS)

AF:

0.187

AC:

947

AN:

5060

South Asian (SAS)

AF:

0.0910

AC:

438

AN:

4812

European-Finnish (FIN)

AF:

0.113

AC:

975

AN:

8656

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0180

AC:

1188

AN:

66024

Other (OTH)

AF:

0.0333

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

230

460

690

920

1150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0294

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.143

AC:

395

AN:

2760

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Colorectal cancer, susceptibility to, 1 (1)

GALNT12-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.3

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.012

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.84

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.93

REVEL

Benign

0.064

Sift

Benign

0.25

Sift4G

Benign

0.41

PromoterAI

-0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.040

gMVP

0.41

Mutation Taster

=97/3

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over