Variant chr4-82917014-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024672.6(THAP9):c.802G>C(p.Glu268Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,582,982 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

THAP9
NM_024672.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2097134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP9	NM_024672.6 linkuse as main transcript	c.802G>C	p.Glu268Gln	missense_variant	5/5	ENST00000302236.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
THAP9	ENST00000302236.10 linkuse as main transcript	c.802G>C	p.Glu268Gln	missense_variant	5/5	1	NM_024672.6	P1
THAP9	ENST00000505901.1 linkuse as main transcript	c.*559G>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	2
THAP9	ENST00000506208.1 linkuse as main transcript	c.*173G>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	3
LIN54	ENST00000505905.1 linkuse as main transcript	n.305-3573C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000443

AC:

AN:

225834

Hom.:

AF XY:

0.00000817

AC XY:

AN XY:

122388

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000945

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1430794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.10e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Aug 09, 2021

The c.802G>C (p.E268Q) alteration is located in exon 5 (coding exon 5) of the THAP9 gene. This alteration results from a G to C substitution at nucleotide position 802, causing the glutamic acid (E) at amino acid position 268 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.00060

Eigen

Benign

-0.0094

Eigen_PC

Benign

-0.090

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.66

M_CAP

Benign

0.0072

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.94

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.16

REVEL

Benign

0.16

Sift

Benign

0.26

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.13

MutPred

0.20

Gain of disorder (P = 0.2017);

MVP

0.25

MPC

0.68

ClinPred

0.29

GERP RS

2.9

Varity_R

0.12

gMVP

0.19

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

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