22-50529755-C-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001113756.3(TYMP):c.-46G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,560,224 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 2 hom. )
Consequence
TYMP
NM_001113756.3 5_prime_UTR_premature_start_codon_gain
NM_001113756.3 5_prime_UTR_premature_start_codon_gain
Scores
2
Splicing: ADA: 0.00003153
2
Clinical Significance
Conservation
PhyloP100: -0.806
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 22-50529755-C-A is Benign according to our data. Variant chr22-50529755-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 379866.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00142 (217/152314) while in subpopulation AFR AF= 0.00488 (203/41572). AF 95% confidence interval is 0.00433. There are 1 homozygotes in gnomad4. There are 103 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TYMP | NM_001953.5 | c.-10-36G>T | intron_variant | ENST00000252029.8 | NP_001944.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TYMP | ENST00000252029.8 | c.-10-36G>T | intron_variant | 1 | NM_001953.5 | ENSP00000252029.3 |
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 217AN: 152196Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000324 AC: 60AN: 185318Hom.: 0 AF XY: 0.000295 AC XY: 30AN XY: 101686
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GnomAD4 exome AF: 0.000135 AC: 190AN: 1407910Hom.: 2 Cov.: 28 AF XY: 0.000124 AC XY: 86AN XY: 696096
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GnomAD4 genome AF: 0.00142 AC: 217AN: 152314Hom.: 1 Cov.: 33 AF XY: 0.00138 AC XY: 103AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 07, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at