chr8-42836712-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_018105.3(THAP1):c.*1250G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000913 in 152,280 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00091 ( 1 hom., cov: 32)
Consequence
THAP1
NM_018105.3 3_prime_UTR
NM_018105.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.704
Genes affected
THAP1 (HGNC:20856): (THAP domain containing 1) The protein encoded by this gene contains a THAP domain, a conserved DNA-binding domain. This protein colocalizes with the apoptosis response protein PAWR/PAR-4 in promyelocytic leukemia (PML) nuclear bodies, and functions as a proapoptotic factor that links PAWR to PML nuclear bodies. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
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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=-0.78).
BP6
Variant 8-42836712-C-T is Benign according to our data. Variant chr8-42836712-C-T is described in ClinVar as [Benign]. Clinvar id is 363106.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000913 (139/152280) while in subpopulation AFR AF= 0.00325 (135/41558). AF 95% confidence interval is 0.0028. There are 1 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 139 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
THAP1 | NM_018105.3 | c.*1250G>A | 3_prime_UTR_variant | 3/3 | ENST00000254250.7 | NP_060575.1 | ||
THAP1 | NM_199003.2 | c.*1534G>A | 3_prime_UTR_variant | 2/2 | NP_945354.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
THAP1 | ENST00000254250.7 | c.*1250G>A | 3_prime_UTR_variant | 3/3 | 1 | NM_018105.3 | ENSP00000254250 | P1 | ||
THAP1 | ENST00000345117.2 | c.*1534G>A | 3_prime_UTR_variant | 2/2 | 1 | ENSP00000344966 |
Frequencies
GnomAD3 genomes AF: 0.000907 AC: 138AN: 152160Hom.: 1 Cov.: 32
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GnomAD4 genome AF: 0.000913 AC: 139AN: 152280Hom.: 1 Cov.: 32 AF XY: 0.000967 AC XY: 72AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Torsion dystonia 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at