Genetic Variant NM_152658.3:c.467C>T (chr19-36039528-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152658.3(THAP8):c.467C>T(p.Thr156Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,556,046 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T156N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 7 hom. )

Consequence

THAP8
NM_152658.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

4 publications found

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:

ENSG00000267698 (HGNC:):

ENSG00000267698 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053763688).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP8	NM_152658.3 link	c.467C>T	p.Thr156Ile	missense_variant	Exon 3 of 4	ENST00000292894.2	NP_689871.1	Q8NA92

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP8	ENST00000292894.2 link	c.467C>T	p.Thr156Ile	missense_variant	Exon 3 of 4	1	NM_152658.3	ENSP00000292894.1		Q8NA92

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

279

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00837

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00195

AC:

349

AN:

178584

AF XY:

0.00192

show subpopulations

Gnomad AFR exome

AF:

0.000772

Gnomad AMR exome

AF:

0.000156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00762

Gnomad NFE exome

AF:

0.00266

Gnomad OTH exome

AF:

0.00158

GnomAD4 exome

AF:

0.00191

AC:

2675

AN:

1403668

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1269

AN XY:

692446

show subpopulations

African (AFR)

AF:

0.000219

AC:

AN:

31942

American (AMR)

AF:

0.000273

AC:

AN:

36638

Ashkenazi Jewish (ASJ)

AF:

0.0000424

AC:

AN:

23562

East Asian (EAS)

AF:

0.00

AC:

AN:

37948

South Asian (SAS)

AF:

0.0000252

AC:

AN:

79224

European-Finnish (FIN)

AF:

0.00776

AC:

392

AN:

50492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00202

AC:

2187

AN:

1080556

Other (OTH)

AF:

0.00132

AC:

AN:

57724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

167

334

501

668

835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00183

AC:

279

AN:

152378

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.000553

AC:

AN:

41598

American (AMR)

AF:

0.000196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00837

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00228

AC:

155

AN:

68040

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000504

Hom.:

Bravo

AF:

0.00119

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00174

AC:

209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.4

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.016

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.69

PhyloP100

1.5

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.96

REVEL

Benign

0.050

Sift

Uncertain

0.0060

Sift4G

Benign

0.11

Polyphen

0.14

Vest4

0.10

MVP

0.69

MPC

0.075

ClinPred

0.012

GERP RS

2.2

Varity_R

0.043

gMVP

0.17

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_152658.3:c.467C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over