Variant 16-67842865-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020457.3(THAP11):c.311A>G(p.Gln104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,608,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

THAP11
NM_020457.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.890

Variant links:

Genes affected

THAP11 (HGNC:23194): (THAP domain containing 11) The protein encoded by this gene contains a THAP domain, which is a conserved DNA-binding domain that has striking similarity to the site-specific DNA-binding domain (DBD) of Drosophila P element transposases. [provided by RefSeq, Jul 2008]

THAP11 links:

CENPT (HGNC:25787): (centromere protein T) The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). CENPT is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).[supplied by OMIM, Mar 2008]

CENPT links:

CENPT (HGNC:):

CENPT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14298707).

BS2

High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP11	NM_020457.3 linkuse as main transcript	c.311A>G	p.Gln104Arg	missense_variant	1/1	ENST00000303596.3	NP_065190.2	Q96EK4
CENPT	NM_025082.4 linkuse as main transcript	c.-492+4536T>C		intron_variant		ENST00000562787.6	NP_079358.3	Q96BT3-1B3KPB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP11	ENST00000303596.3 linkuse as main transcript	c.311A>G	p.Gln104Arg	missense_variant	1/1	6	NM_020457.3	ENSP00000304689.1		Q96EK4
CENPT	ENST00000562787.6 linkuse as main transcript	c.-492+4536T>C		intron_variant		2	NM_025082.4	ENSP00000457810.1		Q96BT3-1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151686

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000208

AC:

AN:

240436

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

131990

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:

0.0000468

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1457302

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

725090

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:

0.0000288

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151686

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74090

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000250

AC:

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

Nov 10, 2022

The c.311A>G (p.Q104R) alteration is located in exon 1 (coding exon 1) of the THAP11 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the glutamine (Q) at amino acid position 104 to be replaced by an arginine (R). 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

0.23

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.28

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.020

REVEL

Benign

0.082

Sift

Benign

1.0

Sift4G

Uncertain

0.048

Polyphen

0.0050

Vest4

0.24

MutPred

0.28

Gain of MoRF binding (P = 0.0384);

MVP

0.85

MPC

1.2

ClinPred

0.059

GERP RS

4.0

Varity_R

0.13

gMVP

0.63

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