rs1064792887
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001953.5(TYMP):c.720delC(p.Val241SerfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A240A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
TYMP
NM_001953.5 frameshift
NM_001953.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.02
Publications
0 publications found
Genes affected
TYMP (HGNC:3148): (thymidine phosphorylase) This gene encodes an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells. Mutations in this gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Apr 2012]
TYMP Gene-Disease associations (from GenCC):
- mitochondrial diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- mitochondrial DNA depletion syndrome 1Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- mitochondrial neurogastrointestinal encephalomyopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 22-50527209-CG-C is Pathogenic according to our data. Variant chr22-50527209-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 223080.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TYMP | NM_001953.5 | c.720delC | p.Val241SerfsTer22 | frameshift_variant | Exon 6 of 10 | ENST00000252029.8 | NP_001944.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TYMP | ENST00000252029.8 | c.720delC | p.Val241SerfsTer22 | frameshift_variant | Exon 6 of 10 | 1 | NM_001953.5 | ENSP00000252029.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461196Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726920 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461196
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
726920
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
52834
Middle Eastern (MID)
AF:
AC:
0
AN:
5732
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111976
Other (OTH)
AF:
AC:
0
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
2
2
3
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
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mitochondrial DNA depletion syndrome 1 Pathogenic:1
Jan 14, 2016
GeneReviews
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.