rs535722487
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000209.4(PDX1):c.312C>A(p.Ala104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,593,382 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: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
PDX1
NM_000209.4 synonymous
NM_000209.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.23
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP7
Synonymous conserved (PhyloP=-2.23 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PDX1 | NM_000209.4 | c.312C>A | p.Ala104= | synonymous_variant | 1/2 | ENST00000381033.5 | NP_000200.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PDX1 | ENST00000381033.5 | c.312C>A | p.Ala104= | synonymous_variant | 1/2 | 1 | NM_000209.4 | ENSP00000370421 | P1 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000955 AC: 2AN: 209510Hom.: 0 AF XY: 0.00000872 AC XY: 1AN XY: 114698
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GnomAD4 exome AF: 0.0000132 AC: 19AN: 1441222Hom.: 0 Cov.: 33 AF XY: 0.0000168 AC XY: 12AN XY: 714974
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GnomAD4 genome 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74310
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ClinVar
Not reported inComputational scores
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Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at