Variant chr1-6632851-C-A 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_001195753.2(THAP3):c.494C>A(p.Ala165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,460,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

THAP3
NM_001195753.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.30

Variant links:

Genes affected

THAP3 (HGNC:20855): (THAP domain containing 3) Predicted to enable DNA binding activity and metal ion binding activity. Involved in positive regulation of transcription by RNA polymerase II. [provided by Alliance of Genome Resources, Apr 2022]

THAP3 links:

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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=0.08203912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP3	NM_001195753.2 linkuse as main transcript	c.494C>A	p.Ala165Glu	missense_variant	6/6	ENST00000054650.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THAP3	ENST00000054650.9 linkuse as main transcript	c.494C>A	p.Ala165Glu	missense_variant	6/6	1	NM_001195753.2	P4	Q8WTV1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000828

AC:

AN:

241524

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132630

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:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460588

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726592

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:

0.0000198

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000854

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jan 24, 2024

The c.494C>A (p.A165E) alteration is located in exon 6 (coding exon 5) of the THAP3 gene. This alteration results from a C to A substitution at nucleotide position 494, causing the alanine (A) at amino acid position 165 to be replaced by a glutamic acid (E). 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

0.097

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.17

DANN

Benign

0.74

DEOGEN2

Benign

0.0079

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.10

Sift

Benign

0.13

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.24

B;B

Vest4

0.10

MutPred

0.24

Gain of solvent accessibility (P = 0.0246);.;

MVP

0.68

MPC

0.41

ClinPred

0.045

GERP RS

-0.80

Varity_R

0.097

gMVP

0.094

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