8-42837681-T-TA

Position:

• chr8-42837681-T-TA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The ENST00000254250.7(THAP1):​c.*280_*281insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 209,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (0 hom.)
• Consequence: THAP1 ENST00000254250.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.376

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000556 (84/151040) while in subpopulation EAS AF= 0.00271 (14/5162). AF 95% confidence interval is 0.00164. There are 0 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP1	NM_018105.3	c.*280_*281insT		3_prime_UTR_variant	3/3	ENST00000254250.7	NP_060575.1
THAP1	NM_199003.2	c.*564_*565insT		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.*280_*281insT		3_prime_UTR_variant	3/3	1	NM_018105.3	ENSP00000254250	P1
THAP1	ENST00000345117.2	c.*564_*565insT		3_prime_UTR_variant	2/2	1		ENSP00000344966

Frequencies

GnomAD3 genomes AF: 0.000557 AC: 84 AN: 150928 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00205

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00294 AC: 172 AN: 58472 Hom.: 0 Cov.: 0 AF XY: 0.00280 AC XY: 89 AN XY: 31772

Gnomad4 AFR exome AF: 0.00518

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.00273

Gnomad4 EAS exome AF: 0.00855

Gnomad4 SAS exome AF: 0.00404

Gnomad4 FIN exome AF: 0.00137

Gnomad4 NFE exome AF: 0.00241

Gnomad4 OTH exome AF: 0.00323

GnomAD4 genome AF: 0.000556 AC: 84 AN: 151040 Hom.: 0 Cov.: 33 AF XY: 0.000704 AC XY: 52 AN XY: 73834

Gnomad4 AFR AF: 0.000727

Gnomad4 AMR AF: 0.00205

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dystonic disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886062946; hg19: chr8-42692824;