rs17296280
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001177306.2(PAM):c.2486-88A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 843,236 control chromosomes in the GnomAD database, including 39,938 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.27 ( 6175 hom., cov: 31)
Exomes 𝑓: 0.31 ( 33763 hom. )
Consequence
PAM
NM_001177306.2 intron
NM_001177306.2 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0440
Genes affected
PAM (HGNC:8596): (peptidylglycine alpha-amidating monooxygenase) This gene encodes a multifunctional protein. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme includes two domains with distinct catalytic activities, a peptidylglycine alpha-hydroxylating monooxygenase (PHM) domain and a peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) domain. These catalytic domains work sequentially to catalyze the conversion of neuroendocrine peptides to active alpha-amidated products. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAM | NM_001177306.2 | c.2486-88A>C | intron_variant | ENST00000438793.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAM | ENST00000438793.8 | c.2486-88A>C | intron_variant | 1 | NM_001177306.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.274 AC: 41635AN: 151722Hom.: 6177 Cov.: 31
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GnomAD4 exome AF: 0.305 AC: 210930AN: 691396Hom.: 33763 AF XY: 0.300 AC XY: 109186AN XY: 364556
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GnomAD4 genome ? AF: 0.274 AC: 41646AN: 151840Hom.: 6175 Cov.: 31 AF XY: 0.271 AC XY: 20104AN XY: 74196
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ClinVar
Not reported inComputational scores
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Calibrated prediction
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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