7-127610566-TGTGTGC-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_001366110.1(PAX4):c.*492_*497del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 293,646 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0083 ( 7 hom., cov: 18)
Exomes 𝑓: 0.00056 ( 0 hom. )
Consequence
PAX4
NM_001366110.1 3_prime_UTR
NM_001366110.1 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.431
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00828 (772/93208) while in subpopulation AFR AF= 0.0312 (720/23084). AF 95% confidence interval is 0.0293. There are 7 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 772 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAX4 | NM_001366110.1 | c.*492_*497del | 3_prime_UTR_variant | 12/12 | ENST00000639438.3 | NP_001353039.1 | ||
PAX4 | NM_001366111.1 | c.*280_*285del | 3_prime_UTR_variant | 10/10 | NP_001353040.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAX4 | ENST00000639438.3 | c.*492_*497del | 3_prime_UTR_variant | 12/12 | 5 | NM_001366110.1 | ENSP00000491782 | A2 | ||
PAX4 | ENST00000341640.6 | c.*492_*497del | 3_prime_UTR_variant | 9/9 | 1 | ENSP00000339906 |
Frequencies
GnomAD3 genomes AF: 0.00825 AC: 768AN: 93136Hom.: 7 Cov.: 18
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GnomAD4 exome AF: 0.000559 AC: 112AN: 200438Hom.: 0 AF XY: 0.000462 AC XY: 49AN XY: 106156
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GnomAD4 genome AF: 0.00828 AC: 772AN: 93208Hom.: 7 Cov.: 18 AF XY: 0.00804 AC XY: 364AN XY: 45292
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Maturity onset diabetes mellitus in young Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at