2-218813096-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000784.4(CYP27A1):c.1017G>T(p.Thr339=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T339T) has been classified as Pathogenic.
Frequency
Consequence
NM_000784.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP27A1 | NM_000784.4 | c.1017G>T | p.Thr339= | splice_region_variant, synonymous_variant | 5/9 | ENST00000258415.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP27A1 | ENST00000258415.9 | c.1017G>T | p.Thr339= | splice_region_variant, synonymous_variant | 5/9 | 1 | NM_000784.4 | P1 | |
CYP27A1 | ENST00000466602.1 | n.1139G>T | splice_region_variant, non_coding_transcript_exon_variant | 2/3 | 2 | ||||
CYP27A1 | ENST00000494263.5 | n.1451G>T | splice_region_variant, non_coding_transcript_exon_variant | 5/7 | 2 | ||||
CYP27A1 | ENST00000445971.1 | c.*478G>T | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1455552Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 723124
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cholestanol storage disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 18, 2018 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2024 | Occurs in the last base pair of the exon Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at