chr1-230178266-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004481.5(GALNT2):​c.175A>G​(p.Ser59Gly) 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. 15/21 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)

Consequence

GALNT2
NM_004481.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11327553).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GALNT2NM_004481.5 linkuse as main transcriptc.175A>G p.Ser59Gly missense_variant 2/16 ENST00000366672.5
GALNT2NM_001291866.2 linkuse as main transcriptc.61A>G p.Ser21Gly missense_variant 2/16
GALNT2XM_017000964.3 linkuse as main transcriptc.82A>G p.Ser28Gly missense_variant 3/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GALNT2ENST00000366672.5 linkuse as main transcriptc.175A>G p.Ser59Gly missense_variant 2/161 NM_004481.5 P1Q10471-1
GALNT2ENST00000494106.1 linkuse as main transcriptn.138A>G non_coding_transcript_exon_variant 2/75

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 08, 2023The c.175A>G (p.S59G) alteration is located in exon 2 (coding exon 2) of the GALNT2 gene. This alteration results from a A to G substitution at nucleotide position 175, causing the serine (S) at amino acid position 59 to be replaced by a glycine (G). 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
Benign
0.059
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
0.90
D;D;D
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.55
N
REVEL
Benign
0.048
Sift
Benign
0.25
T
Sift4G
Benign
0.20
T
Polyphen
0.0080
B
Vest4
0.21
MutPred
0.22
Loss of phosphorylation at S59 (P = 0.0435);
MVP
0.70
MPC
0.50
ClinPred
0.45
T
GERP RS
3.4
Varity_R
0.053
gMVP
0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1663049535; hg19: chr1-230314012; API