rs138345513

Positions:

chr8-42838183-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 2P and 18B. PM1BP4_ModerateBP6_Very_StrongBS1BS2

The NM_018105.3(THAP1):c.421G>A(p.Asp141Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000812 in 1,614,102 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

THAP1
NM_018105.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: 6.77

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 -16 ACMG points.

PM1

In a coiled_coil_region (size 51) in uniprot entity THAP1_HUMAN there are 12 pathogenic changes around while only 1 benign (92%) in NM_018105.3

BP4

Computational evidence support a benign effect (MetaRNN=0.07263759).

BP6

Variant 8-42838183-C-T is Benign according to our data. Variant chr8-42838183-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 448685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000407 (62/152214) while in subpopulation AFR AF= 0.0014 (58/41532). AF 95% confidence interval is 0.00111. There are 0 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP1	NM_018105.3 linkuse as main transcript	c.421G>A	p.Asp141Asn	missense_variant	3/3	ENST00000254250.7
THAP1	NM_199003.2 linkuse as main transcript	c.*63G>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.421G>A	p.Asp141Asn	missense_variant	3/3	1	NM_018105.3	P1	Q9NVV9-1
THAP1	ENST00000345117.2 linkuse as main transcript	c.*63G>A		3_prime_UTR_variant	2/2	1			Q9NVV9-2
THAP1	ENST00000529779.1 linkuse as main transcript	c.316G>A	p.Asp106Asn	missense_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251490

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000407

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000793

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multiple mitochondrial dysfunctions syndrome 9b

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 16, 2024

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 26, 2016

- -

Torsion dystonia 6

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.073

T;T

MetaSVM

Pathogenic

0.89

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.7

D;N

REVEL

Uncertain

0.46

Sift

Benign

0.31

T;T

Sift4G

Benign

0.27

T;T

Polyphen

1.0

D;.

Vest4

0.68

MVP

0.76

MPC

1.5

ClinPred

0.059

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.60

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