rs1718301
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000277.3(PAH):c.441+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,267,994 control chromosomes in the GnomAD database, including 111,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.38 ( 11349 hom., cov: 30)
Exomes 𝑓: 0.41 ( 99780 hom. )
Consequence
PAH
NM_000277.3 intron
NM_000277.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.57
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 12-102877415-G-A is Benign according to our data. Variant chr12-102877415-G-A is described in ClinVar as [Benign]. Clinvar id is 102673.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr12-102877415-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.441+47C>T | intron_variant | ENST00000553106.6 | |||
LOC124902999 | XR_007063428.1 | n.808-2464G>A | intron_variant, non_coding_transcript_variant | ||||
PAH | NM_001354304.2 | c.441+47C>T | intron_variant | ||||
PAH | XM_017019370.2 | c.441+47C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.441+47C>T | intron_variant | 1 | NM_000277.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.376 AC: 56924AN: 151588Hom.: 11340 Cov.: 30
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GnomAD3 exomes AF: 0.372 AC: 93499AN: 251282Hom.: 19054 AF XY: 0.379 AC XY: 51498AN XY: 135814
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GnomAD4 exome AF: 0.414 AC: 462000AN: 1116288Hom.: 99780 Cov.: 15 AF XY: 0.413 AC XY: 236451AN XY: 572126
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GnomAD4 genome ? AF: 0.375 AC: 56951AN: 151706Hom.: 11349 Cov.: 30 AF XY: 0.378 AC XY: 27999AN XY: 74090
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ClinVar
Significance: Benign
Submissions summary: Benign:6Other:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Phenylketonuria Benign:4
Benign, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Dec 09, 2022 | This c.441+47C>T variant in PAH is widely found in population databases at a frequency of 0.372401 in ExAC. This intronic variant is not predicted to have a splice-altering consequence. In summary, this variant meets criteria to be classified as a benign for PAH. PAH-specific ACMG/AMP criteria applied: BP7, BA1. - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 27, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jul 01, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
not provided Benign:1Other: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 | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at