rs1554809253
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001114753.3(ENG):c.1582_1583del(p.Pro528AlafsTer38) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P528P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001114753.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.1582_1583del | p.Pro528AlafsTer38 | frameshift_variant | 12/15 | ENST00000373203.9 | |
LOC102723566 | NR_136302.1 | n.1378-87_1378-86del | intron_variant, non_coding_transcript_variant | ||||
ENG | NM_000118.4 | c.1582_1583del | p.Pro528AlafsTer38 | frameshift_variant | 12/14 | ||
ENG | NM_001278138.2 | c.1036_1037del | p.Pro346AlafsTer38 | frameshift_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.1582_1583del | p.Pro528AlafsTer38 | frameshift_variant | 12/15 | 1 | NM_001114753.3 | P2 | |
ENST00000439298.5 | n.1378-87_1378-86del | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461872Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727242
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2018 | PVS1+PM2+PP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at