8-63065924-TCT-TACTTAC
Position:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000370.3(TTPA):c.530_531delinsGTAAGT(p.Lys177SerfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. K177K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
TTPA
NM_000370.3 frameshift
NM_000370.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.12
Genes affected
TTPA (HGNC:12404): (alpha tocopherol transfer protein) This gene encodes a soluble protein that binds alpha-trocopherol, a form of vitamin E, with high selectivity and affinity. This protein plays an important role in regulating vitamin E levels in the body by transporting vitamin E between membrane vesicles and facilitating the secretion of vitamin E from hepatocytes to circulating lipoproteins. Mutations in this gene cause hereditary vitamin E deficiency (ataxia with vitamin E deficiency, AVED) and retinitis pigmentosa. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-63065925-CT-ACTTAC is Pathogenic according to our data. Variant chr8-63065925-CT-ACTTAC is described in ClinVar as [Pathogenic]. Clinvar id is 65595.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTPA | NM_000370.3 | c.530_531delinsGTAAGT | p.Lys177SerfsTer3 | frameshift_variant | 3/5 | ENST00000260116.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTPA | ENST00000260116.5 | c.530_531delinsGTAAGT | p.Lys177SerfsTer3 | frameshift_variant | 3/5 | 1 | NM_000370.3 | P1 | |
TTPA | ENST00000521138.1 | n.233-17323_233-17322delinsGTAAGT | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Familial isolated deficiency of vitamin E Pathogenic:1
Pathogenic, no assertion criteria provided | curation | GeneReviews | Jun 27, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at