rs193922351
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000209.4(PDX1):c.-18C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000986 in 1,549,406 control chromosomes in the GnomAD database, including 9 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 0.0049 ( 4 hom., cov: 33)
Exomes 𝑓: 0.00056 ( 5 hom. )
Consequence
PDX1
NM_000209.4 5_prime_UTR
NM_000209.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.135
Genes affected
PDX1 (HGNC:6107): (pancreatic and duodenal homeobox 1) The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2. The encoded nuclear protein is involved in the early development of the pancreas and plays a major role in glucose-dependent regulation of insulin gene expression. Defects in this gene are a cause of pancreatic agenesis, which can lead to early-onset insulin-dependent diabetes mellitus (IDDM), as well as maturity onset diabetes of the young type 4 (MODY4). [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 13-27920121-C-T is Benign according to our data. Variant chr13-27920121-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 36402.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=1}.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00492 (750/152348) while in subpopulation AFR AF= 0.0161 (671/41588). AF 95% confidence interval is 0.0151. There are 4 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDX1 | NM_000209.4 | c.-18C>T | 5_prime_UTR_variant | 1/2 | ENST00000381033.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDX1 | ENST00000381033.5 | c.-18C>T | 5_prime_UTR_variant | 1/2 | 1 | NM_000209.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00491 AC: 748AN: 152232Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.00122 AC: 176AN: 144478Hom.: 0 AF XY: 0.00106 AC XY: 83AN XY: 78214
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GnomAD4 exome AF: 0.000556 AC: 777AN: 1397058Hom.: 5 Cov.: 33 AF XY: 0.000495 AC XY: 341AN XY: 689014
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GnomAD4 genome ? AF: 0.00492 AC: 750AN: 152348Hom.: 4 Cov.: 33 AF XY: 0.00542 AC XY: 404AN XY: 74496
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 25, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 14, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Maturity-onset diabetes of the young type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing;curation | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at