Variant 19-36039528-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152658.3(THAP8):c.467C>A(p.Thr156Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,556,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

THAP8
NM_152658.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.00634405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP8	NM_152658.3 linkuse as main transcript	c.467C>A	p.Thr156Asn	missense_variant	3/4	ENST00000292894.2	NP_689871.1
LOC101927572	NR_170988.1 linkuse as main transcript	n.386-11297G>T		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.467C>A	p.Thr156Asn	missense_variant	3/4	1	NM_152658.3	ENSP00000292894	P1
	ENST00000586962.1 linkuse as main transcript	n.380-6181G>T		intron_variant, non_coding_transcript_variant		1
THAP8	ENST00000522483.2 linkuse as main transcript	c.*76C>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	2		ENSP00000429629
THAP8	ENST00000607730.1 linkuse as main transcript	c.*327C>A		3_prime_UTR_variant, NMD_transcript_variant	3/3	3		ENSP00000475450

Frequencies

GnomAD3 genomes

AF:

0.000637

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000274

AC:

AN:

178584

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

96428

show subpopulations

Gnomad AFR exome

AF:

0.00257

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00165

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000453

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000389

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.000123

AC:

172

AN:

1403672

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

692450

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.000109

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000925

Gnomad4 OTH exome

AF:

0.000520

GnomAD4 genome

AF:

0.000630

AC:

AN:

152378

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.0000719

Hom.:

Bravo

AF:

0.000827

ExAC

AF:

0.000250

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.467C>A (p.T156N) alteration is located in exon 3 (coding exon 3) of the THAP8 gene. This alteration results from a C to A substitution at nucleotide position 467, causing the threonine (T) at amino acid position 156 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.4

DANN

Benign

0.94

DEOGEN2

Benign

0.016

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.40

M_CAP

Benign

0.079

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.98

REVEL

Benign

0.11

Sift

Uncertain

0.011

Sift4G

Uncertain

0.020

Polyphen

0.40

Vest4

0.086

MVP

0.69

MPC

0.16

ClinPred

0.0072

GERP RS

2.2

Varity_R

0.057

gMVP

0.11

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