Genetic Variant NM_004481.5:c.31T>A (chr1-230067311-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004481.5(GALNT2):c.31T>A(p.Phe11Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GALNT2
NM_004481.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Publications

0 publications found

Variant links:

Genes affected

GALNT2 (HGNC:4124): (polypeptide N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 2 protein family. Members of this family initiate mucin-type O-glycoslation of peptides in the Golgi apparatus. The encoded protein may be involved in O-linked glycosylation of the immunoglobulin A1 hinge region. This gene may influence triglyceride levels, and may be involved Type 2 diabetes, as well as several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GALNT2 Gene-Disease associations (from GenCC):

congenital disorder of glycosylation, type iit
Inheritance: AR Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

GALNT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3769465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5 link	c.31T>A	p.Phe11Ile	missense_variant	Exon 1 of 16	ENST00000366672.5	NP_004472.1	Q10471-1A0A1L7NY50
GALNT2	NR_120373.2 link	n.74T>A		non_coding_transcript_exon_variant	Exon 1 of 2
GALNT2	NM_001291866.2 link	c.12+9233T>A		intron_variant	Intron 1 of 15		NP_001278795.1	Q10471G3V1S6B7Z6K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT2	ENST00000366672.5 link	c.31T>A	p.Phe11Ile	missense_variant	Exon 1 of 16	1	NM_004481.5	ENSP00000355632.4	Q10471-1
GALNT2	ENST00000488903.1 link	n.53T>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
GALNT2	ENST00000494106.1 link	n.89+9233T>A		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1231140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

607590

African (AFR)

AF:

0.00

AC:

AN:

24594

American (AMR)

AF:

0.00

AC:

AN:

22592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19630

East Asian (EAS)

AF:

0.00

AC:

AN:

24884

South Asian (SAS)

AF:

0.00

AC:

AN:

59580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4532

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

986798

Other (OTH)

AF:

0.00

AC:

AN:

47694

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Mar 30, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.31T>A (p.F11I) alteration is located in exon 1 (coding exon 1) of the GALNT2 gene. This alteration results from a T to A substitution at nucleotide position 31, causing the phenylalanine (F) at amino acid position 11 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.027

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.1

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.72

REVEL

Benign

0.28

Sift

Benign

0.12

Sift4G

Benign

0.17

Polyphen

0.0010

Vest4

0.51

MutPred

0.37

Loss of sheet (P = 0.0181);

MVP

0.82

MPC

0.75

ClinPred

0.71

GERP RS

3.7

PromoterAI

-0.098

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.17

gMVP

0.67

Mutation Taster

=55/45

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over