Genetic Variant GALNT12:p.Met1? (chr9-98807701-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PVS1_ModerateBS2

The NM_024642.5(GALNT12):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,150,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

GALNT12
NM_024642.5 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3O:1

Conservation

PhyloP100: 2.59

Publications

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

GALNT12 links:

ENSG00000285706 (HGNC:):

ENSG00000285706 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 2 pathogenic variants. Next in-frame start position is after 65 codons. Genomic position: 98807891. Lost 0.111 part of the original CDS.

BS2

High AC in GnomAd4 at 47 AD gene.

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.3G>A	p.Met1?	start_lost	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.3G>A	p.Met1?	start_lost	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
GALNT12	ENST00000969913.1		c.3G>A	p.Met1?	start_lost	Exon 1 of 11	ENSP00000639972.1
GALNT12	ENST00000969912.1		c.3G>A	p.Met1?	start_lost	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes

AF:

0.000311

AC:

AN:

150924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

6520

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

999744

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

478320

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

19444

American (AMR)

AF:

0.00

AC:

AN:

5906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10218

East Asian (EAS)

AF:

0.00

AC:

AN:

15418

South Asian (SAS)

AF:

0.00

AC:

AN:

25482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2420

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

869880

Other (OTH)

AF:

0.0000546

AC:

AN:

36644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000311

AC:

AN:

151032

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

73830

show subpopulations

African (AFR)

AF:

0.00109

AC:

AN:

41428

American (AMR)

AF:

0.0000659

AC:

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67646

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.000351

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Colorectal cancer, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Uncertain

0.13

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.99

MetaRNN

Pathogenic

0.87

MetaSVM

Benign

-0.97

PhyloP100

2.6

PROVEAN

Benign

0.22

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.12

Vest4

0.86

MutPred

0.65

Gain of catalytic residue at M1 (P = 0.0188)

MVP

0.52

ClinPred

0.99

GERP RS

3.3

PromoterAI

0.0022

Neutral

(source)

Varity_R

0.88

gMVP

0.49

Mutation Taster

=6/194

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over