15-63305658-T-C
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_031301.4(APH1B):c.651T>C(p.Phe217Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
Consequence
APH1B
NM_031301.4 synonymous
NM_031301.4 synonymous
Scores
2
9
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0410
Genes affected
APH1B (HGNC:24080): (aph-1 homolog B, gamma-secretase subunit) This gene encodes a multi-pass transmembrane protein that is a functional component of the gamma-secretase complex, which also contains presenilin and nicastrin. This protein represents a stabilizing cofactor for the presenilin holoprotein in the complex. The gamma-secretase complex catalyzes the cleavage of integral proteins such as notch receptors and beta-amyloid precursor protein. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14569986).
BP7
Synonymous conserved (PhyloP=-0.041 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APH1B | NM_031301.4 | c.651T>C | p.Phe217Phe | synonymous_variant | Exon 6 of 6 | ENST00000261879.10 | NP_112591.2 | |
APH1B | NM_001145646.2 | c.528T>C | p.Phe176Phe | synonymous_variant | Exon 5 of 5 | NP_001139118.1 | ||
APH1B | XM_024450085.2 | c.489T>C | p.Phe163Phe | synonymous_variant | Exon 6 of 6 | XP_024305853.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
PROVEAN
Benign
N
Sift
Uncertain
D
Sift4G
Uncertain
D
MVP
GERP RS
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