NM_018105.3:c.71+9C>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018105.3(THAP1):c.71+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,610,816 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 7 hom. )

Consequence

THAP1
NM_018105.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.168

Variant links:

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 links:

ENSG00000286837 (HGNC:):

ENSG00000286837 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 8-42843015-G-T is Benign according to our data. Variant chr8-42843015-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 363126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-42843015-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00119 (181/152142) while in subpopulation AMR AF= 0.00262 (40/15296). AF 95% confidence interval is 0.00197. There are 0 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
THAP1	NM_018105.3 link	c.71+9C>A	intron_variant	Intron 1 of 2	ENST00000254250.7	NP_060575.1	Q9NVV9-1
THAP1	NM_199003.2 link	c.71+9C>A	intron_variant	Intron 1 of 1		NP_945354.1	Q9NVV9-2
LOC124901940	XR_007060901.1 link	n.82G>T	non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
THAP1	ENST00000254250.7 link	c.71+9C>A	intron_variant	Intron 1 of 2	1	NM_018105.3	ENSP00000254250.3	Q9NVV9-1
THAP1	ENST00000345117.2 link	c.71+9C>A	intron_variant	Intron 1 of 1	1		ENSP00000344966.2	Q9NVV9-2
THAP1	ENST00000529779.1 link	c.71+9C>A	intron_variant	Intron 1 of 2	5		ENSP00000433912.1	E9PIS9
ENSG00000286837	ENST00000669010.1 link	n.27G>T	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00113

AC:

279

AN:

247066

Hom.:

AF XY:

0.00108

AC XY:

145

AN XY:

134156

show subpopulations

Gnomad AFR exome

AF:

0.000497

Gnomad AMR exome

AF:

0.000613

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000951

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00195

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.00180

AC:

2621

AN:

1458674

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1244

AN XY:

725758

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.000875

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000883

Gnomad4 FIN exome

AF:

0.000245

Gnomad4 NFE exome

AF:

0.00216

Gnomad4 OTH exome

AF:

0.00130

GnomAD4 genome

AF:

0.00119

AC:

181

AN:

152142

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00147

Hom.:

Bravo

AF:

0.00162

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00220

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

THAP1: BS1 -

Sep 03, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31367947, 24936516, 20083799, 27123488) -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Torsion dystonia 6

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Dec 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 07, 2016

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over