NM_000277.3:c.442-18G>A
Variant summary
Our verdict is Uncertain significance. Variant got -1 ACMG points: 0P and 1B. BP7
This summary comes from the ClinGen Evidence Repository: The c.442-18G>A variant in PAH has not been reported in the literature to our knowledge. This variant has a MAF of 0.00067 in the gnomAD Latino population. This is too high for PM2, but too low for BS1 per PAH EP guidelines. No splicing impact is predicted in HSF or MaxEnt (BP7). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA6748923/MONDO:0009861/006
Frequency
Consequence
NM_000277.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.442-18G>A | intron_variant | Intron 4 of 12 | ENST00000553106.6 | NP_000268.1 | ||
PAH | NM_001354304.2 | c.442-18G>A | intron_variant | Intron 5 of 13 | NP_001341233.1 | |||
PAH | XM_017019370.2 | c.442-18G>A | intron_variant | Intron 4 of 6 | XP_016874859.1 | |||
LOC124902999 | XR_007063428.1 | n.807+1454C>T | intron_variant | Intron 1 of 2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.442-18G>A | intron_variant | Intron 4 of 12 | 1 | NM_000277.3 | ENSP00000448059.1 | |||
PAH | ENST00000549111.5 | n.538-18G>A | intron_variant | Intron 4 of 5 | 1 | |||||
PAH | ENST00000307000.7 | c.427-18G>A | intron_variant | Intron 5 of 13 | 5 | ENSP00000303500.2 | ||||
PAH | ENST00000551988.5 | n.530+10781G>A | intron_variant | Intron 4 of 4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000179 AC: 45AN: 251142Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135704
GnomAD4 exome AF: 0.000129 AC: 188AN: 1455350Hom.: 2 Cov.: 29 AF XY: 0.000131 AC XY: 95AN XY: 724452
GnomAD4 genome AF: 0.000151 AC: 23AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74442
ClinVar
Submissions by phenotype
Phenylketonuria Uncertain:1Benign:2
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The c.442-18G>A variant in PAH has not been reported in the literature to our knowledge. This variant has a MAF of 0.00067 in the gnomAD Latino population. This is too high for PM2, but too low for BS1 per PAH EP guidelines. No splicing impact is predicted in HSF or MaxEnt (BP7). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: BP7. -
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not specified Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at