Genetic Variant NM_024642.5:c.356A>G (chr9-98808054-A-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4BS2

The NM_024642.5(GALNT12):c.356A>G(p.Glu119Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,428,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E119V) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

GALNT12
NM_024642.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.07

Publications

14 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36224833).

BS2

High AC in GnomAdExome4 at 5 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	NM_024642.5	MANE Select	c.356A>G	p.Glu119Gly	missense	Exon 1 of 10	NP_078918.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	ENST00000375011.4	TSL:1 MANE Select	c.356A>G	p.Glu119Gly	missense	Exon 1 of 10	ENSP00000364150.3
	GALNT12	ENST00000610463.1	TSL:4	n.50A>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000477657.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000525

AC:

AN:

190346

AF XY:

0.00000961

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000350

AC:

AN:

1428258

Hom.:

Cov.:

AF XY:

0.00000565

AC XY:

AN XY:

707706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33096

American (AMR)

AF:

0.00

AC:

AN:

40770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25468

East Asian (EAS)

AF:

0.00

AC:

AN:

38652

South Asian (SAS)

AF:

0.0000612

AC:

AN:

81710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4644

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098352

Other (OTH)

AF:

0.00

AC:

AN:

59198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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

Cov.:

ExAC

AF:

0.00000851

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

0.067

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.5

PhyloP100

8.1

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.35

Sift

Uncertain

0.011

Sift4G

Uncertain

0.0050

Polyphen

0.0020

Vest4

0.44

MutPred

0.81

Gain of MoRF binding (P = 0.0391)

MVP

0.64

MPC

0.17

ClinPred

0.90

GERP RS

3.7

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.69

gMVP

0.67

Mutation Taster

=57/43

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over