rs55965422
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_ModerateBS2
The NM_000777.5(CYP3A5):c.432+2T>C variant causes a splice donor change. The variant allele was found at a frequency of 0.000173 in 1,613,102 control chromosomes in the GnomAD database, including 1 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 0.00027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
CYP3A5
NM_000777.5 splice_donor
NM_000777.5 splice_donor
Scores
3
2
2
Splicing: ADA: 0.9848
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.57
Genes affected
CYP3A5 (HGNC:2638): (cytochrome P450 family 3 subfamily A member 5) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein metabolizes drugs as well as the steroid hormones testosterone and progesterone. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Two pseudogenes of this gene have been identified within this cluster on chromosome 7. Expression of this gene is widely variable among populations, and a single nucleotide polymorphism that affects transcript splicing has been associated with susceptibility to hypertensions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.07488403 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
BS2
?
High AC in GnomAd at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP3A5 | NM_000777.5 | c.432+2T>C | splice_donor_variant | ENST00000222982.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP3A5 | ENST00000222982.8 | c.432+2T>C | splice_donor_variant | 1 | NM_000777.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000270 AC: 41AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000466 AC: 117AN: 251308Hom.: 0 AF XY: 0.000478 AC XY: 65AN XY: 135842
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GnomAD4 exome AF: 0.000163 AC: 238AN: 1460898Hom.: 1 Cov.: 31 AF XY: 0.000158 AC XY: 115AN XY: 726852
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GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74418
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3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D;D
GERP RS
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at