Genetic Variant GALNT12:c.732-229T>C (chr9-98831543-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024642.5(GALNT12):c.732-229T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,048 control chromosomes in the GnomAD database, including 13,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 13119 hom., cov: 32)

Consequence

GALNT12
NM_024642.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.161

Publications

8 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-98831543-T-C is Benign according to our data. Variant chr9-98831543-T-C is described in ClinVar as Benign. ClinVar VariationId is 1235687.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT12	NM_024642.5 link	c.732-229T>C		intron_variant	Intron 3 of 9	ENST00000375011.4	NP_078918.3	Q8IXK2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4 link	c.732-229T>C		intron_variant	Intron 3 of 9	1	NM_024642.5	ENSP00000364150.3		Q8IXK2-1
GALNT12	ENST00000610463.1 link	n.*163-229T>C		intron_variant	Intron 2 of 3	4		ENSP00000477657.1		A0A087WT76

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62632

AN:

151930

Hom.:

13102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.412

AC:

62700

AN:

152048

Hom.:

13119

Cov.:

AF XY:

0.408

AC XY:

30304

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.497

AC:

20606

AN:

41444

American (AMR)

AF:

0.342

AC:

5224

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1141

AN:

3470

East Asian (EAS)

AF:

0.210

AC:

1086

AN:

5162

South Asian (SAS)

AF:

0.308

AC:

1479

AN:

4808

European-Finnish (FIN)

AF:

0.421

AC:

4454

AN:

10582

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.404

AC:

27452

AN:

67980

Other (OTH)

AF:

0.398

AC:

841

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1858

3716

5574

7432

9290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.394

Hom.:

22346

Bravo

AF:

0.410

Asia WGS

AF:

0.288

AC:

1002

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.69

(source)

DANN

Benign

0.51

PhyloP100

0.16

Mutation Taster

=100/0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over