rs2037639
Positions:
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.353-22C>T variant in PAH has a MAF of 0.7066 in the gnomAD East Asian 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/CA229520/MONDO:0009861/006
Frequency
Genomes: 𝑓 0.22 ( 4517 hom., cov: 31)
Exomes 𝑓: 0.25 ( 48672 hom. )
Consequence
PAH
NM_000277.3 intron
NM_000277.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.216
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP7
?
BA1
?
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.353-22C>T | intron_variant | ENST00000553106.6 | |||
LOC124902999 | XR_007063428.1 | n.808-2307G>A | intron_variant, non_coding_transcript_variant | ||||
PAH | NM_001354304.2 | c.353-22C>T | intron_variant | ||||
PAH | XM_017019370.2 | c.353-22C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.353-22C>T | intron_variant | 1 | NM_000277.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.221 AC: 33548AN: 151976Hom.: 4519 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
33548
AN:
151976
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.274 AC: 68767AN: 250962Hom.: 11705 AF XY: 0.278 AC XY: 37735AN XY: 135654
GnomAD3 exomes
AF:
AC:
68767
AN:
250962
Hom.:
AF XY:
AC XY:
37735
AN XY:
135654
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.247 AC: 352222AN: 1425802Hom.: 48672 Cov.: 26 AF XY: 0.250 AC XY: 178113AN XY: 711592
GnomAD4 exome
AF:
AC:
352222
AN:
1425802
Hom.:
Cov.:
26
AF XY:
AC XY:
178113
AN XY:
711592
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.221 AC: 33549AN: 152092Hom.: 4517 Cov.: 31 AF XY: 0.224 AC XY: 16679AN XY: 74346
GnomAD4 genome
?
AF:
AC:
33549
AN:
152092
Hom.:
Cov.:
31
AF XY:
AC XY:
16679
AN XY:
74346
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1504
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:7Other:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Phenylketonuria Benign:5
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 04, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jul 01, 2021 | - - |
Benign, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Mar 27, 2020 | The c.353-22C>T variant in PAH has a MAF of 0.7066 in the gnomAD East Asian 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 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
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
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at