Variant 19-36039343-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_152658.3(THAP8):c.652C>T(p.Arg218Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,522,678 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

THAP8
NM_152658.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0550

Variant links:

Genes affected

THAP8 (HGNC:23191): (THAP domain containing 8) Predicted to enable DNA binding activity and metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

THAP8 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042548776).

BP6

Variant 19-36039343-G-A is Benign according to our data. Variant chr19-36039343-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2455764.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP8	NM_152658.3 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	3/4	ENST00000292894.2	NP_689871.1
LOC101927572	NR_170988.1 linkuse as main transcript	n.386-11482G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
THAP8	ENST00000292894.2 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	3/4	1	NM_152658.3	ENSP00000292894	P1
	ENST00000586962.1 linkuse as main transcript	n.380-6366G>A		intron_variant, non_coding_transcript_variant		1
THAP8	ENST00000522483.2 linkuse as main transcript	c.*261C>T		3_prime_UTR_variant, NMD_transcript_variant	2/3	2		ENSP00000429629
THAP8	ENST00000607730.1 linkuse as main transcript	c.*512C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	3		ENSP00000475450

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00129

AC:

158

AN:

122250

Hom.:

AF XY:

0.00103

AC XY:

AN XY:

66772

show subpopulations

Gnomad AFR exome

AF:

0.000162

Gnomad AMR exome

AF:

0.00568

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000951

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000218

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000225

AC:

308

AN:

1370300

Hom.:

Cov.:

AF XY:

0.000225

AC XY:

152

AN XY:

675180

show subpopulations

Gnomad4 AFR exome

AF:

0.0000643

Gnomad4 AMR exome

AF:

0.00459

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000966

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000616

Gnomad4 OTH exome

AF:

0.000140

GnomAD4 genome

AF:

0.000171

AC:

AN:

152378

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.000491

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.018

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.64

REVEL

Benign

0.086

Sift

Benign

0.17

Sift4G

Uncertain

0.019

Polyphen

0.0010

Vest4

0.11

MVP

0.23

MPC

0.082

ClinPred

0.018

GERP RS

-1.4

Varity_R

0.056

gMVP

0.055

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