rs587780414
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001366110.1(PAX4):c.515G>A(p.Arg172Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,613,884 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 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
PAX4
NM_001366110.1 missense
NM_001366110.1 missense
Scores
10
5
2
Clinical Significance
Conservation
PhyloP100: 5.23
Genes affected
PAX4 (HGNC:8618): (paired box 4) This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box 4 gene is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.856
BS2
High AC in GnomAdExome4 at 87 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAX4 | NM_001366110.1 | c.515G>A | p.Arg172Gln | missense_variant | 7/12 | ENST00000639438.3 | NP_001353039.1 | |
PAX4 | NM_001366111.1 | c.515G>A | p.Arg172Gln | missense_variant | 5/10 | NP_001353040.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAX4 | ENST00000639438.3 | c.515G>A | p.Arg172Gln | missense_variant | 7/12 | 5 | NM_001366110.1 | ENSP00000491782.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151998Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
3
AN:
151998
Hom.:
Cov.:
31
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: 0.0000437 AC: 11AN: 251464Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135906
GnomAD3 exomes
AF:
AC:
11
AN:
251464
Hom.:
AF XY:
AC XY:
7
AN XY:
135906
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: 0.0000595 AC: 87AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000633 AC XY: 46AN XY: 727242
GnomAD4 exome
AF:
AC:
87
AN:
1461886
Hom.:
Cov.:
33
AF XY:
AC XY:
46
AN XY:
727242
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: 0.0000197 AC: 3AN: 151998Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74244
GnomAD4 genome
AF:
AC:
3
AN:
151998
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
74244
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.:
ExAC
AF:
AC:
5
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 04, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 02, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 164 of the PAX4 protein (p.Arg164Gln). This variant is present in population databases (rs587780414, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PAX4-related conditions. ClinVar contains an entry for this variant (Variation ID: 129874). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. - |
Maturity onset diabetes mellitus in young Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Type 2 diabetes mellitus;C2677132:Maturity-onset diabetes of the young type 9;C3837958:Diabetes mellitus, ketosis-prone Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 04, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;.;.;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D;D;.;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;.;D;D;D;.
Sift4G
Pathogenic
D;.;.;D;D;D
Polyphen
D;.;.;.;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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