dbSNP rs897945: THAP9:p.Leu299Phe (chr4-82917109-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024672.6(THAP9):c.897G>T(p.Leu299Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,612,860 control chromosomes in the GnomAD database, including 231,111 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 16903 hom., cov: 33)

Exomes 𝑓: 0.53 ( 214208 hom. )

Consequence

THAP9
NM_024672.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.354

Publications

38 publications found

Variant links:

Genes affected

THAP9 (HGNC:23192): (THAP domain containing 9) Enables sequence-specific DNA binding activity and transposase activity. Involved in DNA integration and transposition, DNA-mediated. [provided by Alliance of Genome Resources, Apr 2022]

THAP9 links:

LIN54 (HGNC:25397): (lin-54 DREAM MuvB core complex component) LIN54 is a component of the LIN, or DREAM, complex, an essential regulator of cell cycle genes (Schmit et al., 2009 [PubMed 19725879]).[supplied by OMIM, Dec 2010]

LIN54 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9059777E-5).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP9	NM_024672.6 link	c.897G>T	p.Leu299Phe	missense_variant	Exon 5 of 5	ENST00000302236.10	NP_078948.3	Q9H5L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP9	ENST00000302236.10 link	c.897G>T	p.Leu299Phe	missense_variant	Exon 5 of 5	1	NM_024672.6	ENSP00000305533.5		Q9H5L6

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65329

AN:

151986

Hom.:

16889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.579

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.454

GnomAD2 exomes

AF:

0.504

AC:

126049

AN:

250308

AF XY:

0.500

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.704

Gnomad ASJ exome

AF:

0.471

Gnomad EAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.596

Gnomad NFE exome

AF:

0.564

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.531

AC:

776387

AN:

1460756

Hom.:

214208

Cov.:

AF XY:

0.527

AC XY:

382904

AN XY:

726692

show subpopulations

African (AFR)

AF:

0.128

AC:

4285

AN:

33426

American (AMR)

AF:

0.696

AC:

30990

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

12140

AN:

26046

East Asian (EAS)

AF:

0.258

AC:

10228

AN:

39692

South Asian (SAS)

AF:

0.373

AC:

32140

AN:

86138

European-Finnish (FIN)

AF:

0.599

AC:

31934

AN:

53330

Middle Eastern (MID)

AF:

0.378

AC:

2179

AN:

5764

European-Non Finnish (NFE)

AF:

0.561

AC:

623325

AN:

1111520

Other (OTH)

AF:

0.483

AC:

29166

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

20652

41305

61957

82610

103262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17088

34176

51264

68352

85440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.430

AC:

65360

AN:

152104

Hom.:

16903

Cov.:

AF XY:

0.427

AC XY:

31743

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.146

AC:

6046

AN:

41524

American (AMR)

AF:

0.583

AC:

8908

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1606

AN:

3470

East Asian (EAS)

AF:

0.218

AC:

1128

AN:

5178

South Asian (SAS)

AF:

0.353

AC:

1702

AN:

4822

European-Finnish (FIN)

AF:

0.579

AC:

6116

AN:

10554

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.562

AC:

38183

AN:

67974

Other (OTH)

AF:

0.458

AC:

968

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1650

3300

4949

6599

8249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.511

Hom.:

69428

Bravo

AF:

0.423

TwinsUK

AF:

0.572

AC:

2120

ALSPAC

AF:

0.577

AC:

2222

ESP6500AA

AF:

0.151

AC:

666

ESP6500EA

AF:

0.558

AC:

4799

ExAC

AF:

0.493

AC:

59889

Asia WGS

AF:

0.340

AC:

1182

AN:

3478

EpiCase

AF:

0.548

EpiControl

AF:

0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.00046

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.68

MetaRNN

Benign

0.000019

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.73

PhyloP100

0.35

PrimateAI

Benign

0.43

PROVEAN

Benign

2.4

REVEL

Benign

0.11

Sift

Benign

0.50

Sift4G

Pathogenic

0.0

Polyphen

0.91

Vest4

0.11

MutPred

0.10

Loss of helix (P = 0.0558);

MPC

0.52

ClinPred

0.012

GERP RS

2.9

Varity_R

0.060

gMVP

0.50

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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