rs1802642842

Variant names:

• chr8-42837823-T-C
• rs1802642842
• NM_018105.3:c.*139A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018105.3(THAP1):​c.*139A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000267 in 749,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: THAP1 NM_018105.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.560
• Publications: 0 publications found

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]

THAP1 Gene-Disease associations (from GenCC):

• torsion dystonia 6

  Inheritance: AD, SD Classification: STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018105.3. 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
	THAP1	NM_018105.3	MANE Select	c.*139A>G		3_prime_UTR	Exon 3 of 3	NP_060575.1	Q9NVV9-1
	THAP1	NM_199003.2		c.*423A>G		3_prime_UTR	Exon 2 of 2	NP_945354.1	Q9NVV9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP1	ENST00000254250.7	TSL:1 MANE Select	c.*139A>G		3_prime_UTR	Exon 3 of 3	ENSP00000254250.3	Q9NVV9-1
	THAP1	ENST00000345117.2	TSL:1	c.*423A>G		3_prime_UTR	Exon 2 of 2	ENSP00000344966.2	Q9NVV9-2
	THAP1	ENST00000934698.1		c.*139A>G		3_prime_UTR	Exon 3 of 3	ENSP00000604757.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000267 AC: 2 AN: 749086 Hom.: 0 Cov.: 10 AF XY: 0.00000266 AC XY: 1 AN XY: 375708

African (AFR) AF: 0.00 AC: 0 AN: 17206

American (AMR) AF: 0.00 AC: 0 AN: 13506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15054

East Asian (EAS) AF: 0.00 AC: 0 AN: 29636

South Asian (SAS) AF: 0.00 AC: 0 AN: 33798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2544

European-Non Finnish (NFE) AF: 0.00000347 AC: 2 AN: 576858

Other (OTH) AF: 0.00 AC: 0 AN: 34840

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Torsion dystonia 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.1
DANN	Benign	0.85
PhyloP100		0.56

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

Other links and lift over

dbSNP: rs1802642842; hg19: chr8-42692966;