rs201114442
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_032806.6(POMGNT2):c.454G>A(p.Val152Met) variant causes a missense change. The variant allele was found at a frequency of 0.000122 in 1,614,216 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 3 hom. )
Consequence
POMGNT2
NM_032806.6 missense
NM_032806.6 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 4.96
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.023945928).
BP6
?
Variant 3-43080978-C-T is Benign according to our data. Variant chr3-43080978-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 473279.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00019 (29/152338) while in subpopulation EAS AF= 0.00193 (10/5172). AF 95% confidence interval is 0.00105. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMGNT2 | NM_032806.6 | c.454G>A | p.Val152Met | missense_variant | 2/2 | ENST00000344697.3 | |
POMGNT2 | XM_005265515.4 | c.454G>A | p.Val152Met | missense_variant | 3/3 | ||
POMGNT2 | XM_011534163.3 | c.454G>A | p.Val152Met | missense_variant | 3/3 | ||
POMGNT2 | XM_017007353.2 | c.454G>A | p.Val152Met | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMGNT2 | ENST00000344697.3 | c.454G>A | p.Val152Met | missense_variant | 2/2 | 1 | NM_032806.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152220Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
25
AN:
152220
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000219 AC: 55AN: 251410Hom.: 2 AF XY: 0.000258 AC XY: 35AN XY: 135880
GnomAD3 exomes
AF:
AC:
55
AN:
251410
Hom.:
AF XY:
AC XY:
35
AN XY:
135880
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000115 AC: 168AN: 1461878Hom.: 3 Cov.: 37 AF XY: 0.000129 AC XY: 94AN XY: 727238
GnomAD4 exome
AF:
AC:
168
AN:
1461878
Hom.:
Cov.:
37
AF XY:
AC XY:
94
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000190 AC: 29AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74494
GnomAD4 genome
?
AF:
AC:
29
AN:
152338
Hom.:
Cov.:
33
AF XY:
AC XY:
13
AN XY:
74494
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
31
Asia WGS
AF:
AC:
23
AN:
3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 152 of the POMGNT2 protein (p.Val152Met). This variant is present in population databases (rs201114442, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with POMGNT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 473279). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. - |
POMGNT2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 08, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | POMGNT2: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
0.75
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at