GeneBe

7-127613804-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366110.1(PAX4):​c.514C>A​(p.Arg172Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PAX4
NM_001366110.1 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

0 publications found
Variant links:
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]
PAX4 Gene-Disease associations (from GenCC):
  • maturity-onset diabetes of the young
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • diabetes mellitus, noninsulin-dependent
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
  • maturity-onset diabetes of the young type 9
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
  • monogenic diabetes
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAX4NM_001366110.1 linkc.514C>A p.Arg172Arg synonymous_variant Exon 7 of 12 ENST00000639438.3 NP_001353039.1
PAX4NM_001366111.1 linkc.514C>A p.Arg172Arg synonymous_variant Exon 5 of 10 NP_001353040.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAX4ENST00000639438.3 linkc.514C>A p.Arg172Arg synonymous_variant Exon 7 of 12 5 NM_001366110.1 ENSP00000491782.1 A0A1W2PPX4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461878
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727240
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112002
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
7.5
DANN
Benign
0.67
PhyloP100
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.26
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.26
Position offset: -48

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs121917718; hg19: chr7-127253858; API