12-102839190-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000277.3(PAH):c.1344C>T(p.Leu448=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PAH
NM_000277.3 synonymous
NM_000277.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0130
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 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=-0.46).
BP6
?
Variant 12-102839190-G-A is Benign according to our data. Variant chr12-102839190-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1146245.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.013 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.1344C>T | p.Leu448= | synonymous_variant | 13/13 | ENST00000553106.6 | |
PAH | NM_001354304.2 | c.1344C>T | p.Leu448= | synonymous_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.1344C>T | p.Leu448= | synonymous_variant | 13/13 | 1 | NM_000277.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251190Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135766
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461534Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727064
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Phenylketonuria Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 16, 2023 | - - |
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