rs62509021
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP7
This summary comes from the ClinGen Evidence Repository: The c.1316-35C>T variant in PAH has a MAF of 0.02321 in the gnomAD European (Non-Finnish) population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7 LINK:https://erepo.genome.network/evrepo/ui/classification/CA229433/MONDO:0009861/006
Frequency
Genomes: 𝑓 0.017 ( 34 hom., cov: 33)
Exomes 𝑓: 0.022 ( 444 hom. )
Consequence
PAH
ENST00000553106.6 intron
ENST00000553106.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.87
Genes affected
PAH (HGNC:8582): (phenylalanine hydroxylase) This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine and is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP7
For more information check the summary or visit ClinGen Evidence Repository.
BA1
For more information check the summary or visit ClinGen Evidence Repository.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.1316-35C>T | intron_variant | ENST00000553106.6 | NP_000268.1 | |||
PAH | NM_001354304.2 | c.1316-35C>T | intron_variant | NP_001341233.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.1316-35C>T | intron_variant | 1 | NM_000277.3 | ENSP00000448059 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0167 AC: 2543AN: 152168Hom.: 34 Cov.: 33
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GnomAD3 exomes AF: 0.0161 AC: 4031AN: 250524Hom.: 53 AF XY: 0.0168 AC XY: 2283AN XY: 135492
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GnomAD4 exome AF: 0.0223 AC: 32486AN: 1455256Hom.: 444 Cov.: 28 AF XY: 0.0222 AC XY: 16076AN XY: 724472
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GnomAD4 genome AF: 0.0167 AC: 2542AN: 152286Hom.: 34 Cov.: 33 AF XY: 0.0156 AC XY: 1163AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:4Other:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not provided Benign:2Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
not provided, no classification provided | literature only | DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE | - | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Phenylketonuria Benign:1
Benign, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Mar 27, 2020 | The c.1316-35C>T variant in PAH has a MAF of 0.02321 in the gnomAD European (Non-Finnish) population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7 - |
Computational scores
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Name
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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