Variant chr8-42837772-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_018105.3(THAP1):c.*190C>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 0.00144 in 479,086 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

THAP1
NM_018105.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 8-42837772-G-T is Benign according to our data. Variant chr8-42837772-G-T is described in ClinVar as [Benign]. Clinvar id is 363120.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00145 (220/151748) while in subpopulation EAS AF= 0.016 (83/5180). AF 95% confidence interval is 0.0132. There are 0 homozygotes in gnomad4. There are 146 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 220 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP1	NM_018105.3 linkuse as main transcript	c.*190C>A		3_prime_UTR_variant	3/3	ENST00000254250.7
THAP1	NM_199003.2 linkuse as main transcript	c.*474C>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THAP1	ENST00000254250.7 linkuse as main transcript	c.*190C>A		3_prime_UTR_variant	3/3	1	NM_018105.3	P1	Q9NVV9-1
THAP1	ENST00000345117.2 linkuse as main transcript	c.*474C>A		3_prime_UTR_variant	2/2	1			Q9NVV9-2

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

151632

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00936

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000280

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.00143

AC:

468

AN:

327338

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

247

AN XY:

166420

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0105

Gnomad4 SAS exome

AF:

0.000659

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.000236

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00145

AC:

220

AN:

151748

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

146

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0160

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00936

Gnomad4 NFE

AF:

0.000280

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00100

Asia WGS

AF:

0.00995

AC:

AN:

3430

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.79

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

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