chr3-43081420-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1

The NM_032806.6(POMGNT2):​c.12G>A​(p.Ser4Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,571,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S4S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

POMGNT2
NM_032806.6 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -3.06
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 Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 3-43081420-C-T is Benign according to our data. Variant chr3-43081420-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436368.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-3.06 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000108 (153/1418846) while in subpopulation SAS AF= 0.000672 (53/78874). AF 95% confidence interval is 0.000527. There are 0 homozygotes in gnomad4_exome. There are 89 alleles in male gnomad4_exome subpopulation. Median coverage is 37. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POMGNT2NM_032806.6 linkc.12G>A p.Ser4Ser synonymous_variant Exon 2 of 2 ENST00000344697.3 NP_116195.2 Q8NAT1A0A024R2P4
POMGNT2XM_005265515.4 linkc.12G>A p.Ser4Ser synonymous_variant Exon 3 of 3 XP_005265572.1 Q8NAT1A0A024R2P4
POMGNT2XM_011534163.3 linkc.12G>A p.Ser4Ser synonymous_variant Exon 3 of 3 XP_011532465.1 Q8NAT1A0A024R2P4
POMGNT2XM_017007353.2 linkc.12G>A p.Ser4Ser synonymous_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.12G>A p.Ser4Ser synonymous_variant Exon 2 of 2 1 NM_032806.6 ENSP00000344125.2 Q8NAT1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000176
AC:
36
AN:
204806
Hom.:
0
AF XY:
0.000190
AC XY:
21
AN XY:
110286
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000177
Gnomad SAS exome
AF:
0.00104
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000107
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000108
AC:
153
AN:
1418846
Hom.:
0
Cov.:
37
AF XY:
0.000127
AC XY:
89
AN XY:
701790
show subpopulations
Gnomad4 AFR exome
AF:
0.0000930
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000153
Gnomad4 SAS exome
AF:
0.000672
Gnomad4 FIN exome
AF:
0.0000204
Gnomad4 NFE exome
AF:
0.0000778
Gnomad4 OTH exome
AF:
0.0000684
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152306
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000869
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 25, 2015
Genetic Services Laboratory, University of Chicago
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Benign:1
Nov 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:1
Jul 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

POMGNT2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.060
DANN
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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: rs368531523; hg19: chr3-43122912; COSMIC: COSV60954421; API