rs778907895

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032806.6(POMGNT2):​c.332G>A​(p.Arg111His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,046 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

POMGNT2
NM_032806.6 missense

Scores

9
3
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
POMGNT2 (HGNC:25902): (protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-)) This gene encodes a protein with glycosyltransferase activity although its function is not currently known. [provided by RefSeq, Sep 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POMGNT2NM_032806.6 linkc.332G>A p.Arg111His missense_variant Exon 2 of 2 ENST00000344697.3 NP_116195.2 Q8NAT1A0A024R2P4
POMGNT2XM_005265515.4 linkc.332G>A p.Arg111His missense_variant Exon 3 of 3 XP_005265572.1 Q8NAT1A0A024R2P4
POMGNT2XM_011534163.3 linkc.332G>A p.Arg111His missense_variant Exon 3 of 3 XP_011532465.1 Q8NAT1A0A024R2P4
POMGNT2XM_017007353.2 linkc.332G>A p.Arg111His missense_variant Exon 4 of 4 XP_016862842.1 Q8NAT1A0A024R2P4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POMGNT2ENST00000344697.3 linkc.332G>A p.Arg111His missense_variant Exon 2 of 2 1 NM_032806.6 ENSP00000344125.2 Q8NAT1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251436
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461882
Hom.:
0
Cov.:
37
AF XY:
0.0000110
AC XY:
8
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152164
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Uncertain:1
Feb 03, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ClinVar contains an entry for this variant (Variation ID: 540495). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 111 of the POMGNT2 protein (p.Arg111His). This variant is present in population databases (rs778907895, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POMGNT2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.12
T;T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
.;D
M_CAP
Benign
0.072
D
MetaRNN
Pathogenic
0.92
D;D
MetaSVM
Uncertain
0.25
D
MutationAssessor
Benign
1.8
L;L
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.1
N;N
REVEL
Pathogenic
0.76
Sift
Benign
0.097
T;T
Sift4G
Benign
0.11
T;T
Polyphen
1.0
D;D
Vest4
0.84
MutPred
0.83
Loss of methylation at R111 (P = 0.1);Loss of methylation at R111 (P = 0.1);
MVP
0.80
MPC
1.0
ClinPred
0.47
T
GERP RS
5.9
Varity_R
0.15
gMVP
0.63

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: rs778907895; hg19: chr3-43122592; COSMIC: COSV100768157; API