rs1553926818
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000253.4(MTTP):c.708_709delCA(p.His236GlnfsTer11) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MTTP
NM_000253.4 frameshift
NM_000253.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.00
Publications
1 publications found
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]
MTTP Gene-Disease associations (from GenCC):
- abetalipoproteinemiaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 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 4-99591734-AAC-A is Pathogenic according to our data. Variant chr4-99591734-AAC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 435905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000253.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MTTP | NM_001386140.1 | MANE Select | c.708_709delCA | p.His236GlnfsTer11 | frameshift | Exon 6 of 18 | NP_001373069.1 | ||
| MTTP | NM_000253.4 | c.708_709delCA | p.His236GlnfsTer11 | frameshift | Exon 7 of 19 | NP_000244.2 | |||
| MTTP | NM_001300785.2 | c.459_460delCA | p.His153GlnfsTer11 | frameshift | Exon 6 of 18 | NP_001287714.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MTTP | ENST00000265517.10 | TSL:1 MANE Select | c.708_709delCA | p.His236GlnfsTer11 | frameshift | Exon 6 of 18 | ENSP00000265517.5 | ||
| MTTP | ENST00000457717.6 | TSL:5 | c.708_709delCA | p.His236GlnfsTer11 | frameshift | Exon 7 of 19 | ENSP00000400821.1 | ||
| MTTP | ENST00000511045.6 | TSL:2 | c.459_460delCA | p.His153GlnfsTer11 | frameshift | Exon 6 of 18 | ENSP00000427679.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461122Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726874 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461122
Hom.:
AF XY:
AC XY:
0
AN XY:
726874
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33462
American (AMR)
AF:
AC:
0
AN:
44696
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26108
East Asian (EAS)
AF:
AC:
0
AN:
39624
South Asian (SAS)
AF:
AC:
0
AN:
86216
European-Finnish (FIN)
AF:
AC:
0
AN:
53382
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111520
Other (OTH)
AF:
AC:
0
AN:
60350
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
Abetalipoproteinaemia (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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