4-99574921-T-TG
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001386140.1(MTTP):c.13dup(p.Ala5GlyfsTer16) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
MTTP
NM_001386140.1 frameshift
NM_001386140.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.83
Genes affected
MTTP (HGNC:7467): (microsomal triglyceride transfer protein) MTP encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein. Protein disulfide isomerase (PDI) completes the heterodimeric microsomal triglyceride transfer protein, which has been shown to play a central role in lipoprotein assembly. Mutations in MTP can cause abetalipoproteinemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 106 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-99574921-T-TG is Pathogenic according to our data. Variant chr4-99574921-T-TG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1711595.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTTP | NM_001386140.1 | c.13dup | p.Ala5GlyfsTer16 | frameshift_variant | 1/18 | ENST00000265517.10 | |
MTTP | NM_000253.4 | c.13dup | p.Ala5GlyfsTer16 | frameshift_variant | 2/19 | ||
MTTP | NM_001300785.2 | c.-188-6983dup | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTTP | ENST00000265517.10 | c.13dup | p.Ala5GlyfsTer16 | frameshift_variant | 1/18 | 1 | NM_001386140.1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | MTTP: PVS1:Strong, PM2 - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.