Variant 16-67842866-GCAGCAGCAACAGCAGCAGCAGCAGCAA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_020457.3(THAP11):c.348_374delACAGCAGCAGCAGCAGCAACAGCAGCA(p.Gln117_Gln125del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000782 in 150,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

THAP11
NM_020457.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_020457.3

BS2

High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP11	NM_020457.3 link	c.348_374delACAGCAGCAGCAGCAGCAACAGCAGCA	p.Gln117_Gln125del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000303596.3	NP_065190.2	Q96EK4
CENPT	NM_025082.4 link	c.-492+4508_-492+4534delTTGCTGCTGCTGCTGCTGTTGCTGCTG		intron_variant	Intron 1 of 15	ENST00000562787.6	NP_079358.3	Q96BT3-1B3KPB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP11	ENST00000303596.3 link	c.348_374delACAGCAGCAGCAGCAGCAACAGCAGCA	p.Gln117_Gln125del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_020457.3	ENSP00000304689.1		Q96EK4
CENPT	ENST00000562787.6 link	c.-492+4508_-492+4534delTTGCTGCTGCTGCTGCTGTTGCTGCTG		intron_variant	Intron 1 of 15	2	NM_025082.4	ENSP00000457810.1		Q96BT3-1

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

119

AN:

150872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000791

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000584

Gnomad SAS

AF:

0.00399

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000785

Gnomad OTH

AF:

0.000483

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000752

AC:

1094

AN:

1455544

Hom.:

AF XY:

0.000880

AC XY:

637

AN XY:

724230

show subpopulations

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.000359

Gnomad4 ASJ exome

AF:

0.00430

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00446

Gnomad4 FIN exome

AF:

0.000290

Gnomad4 NFE exome

AF:

0.000432

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.000782

AC:

118

AN:

150978

Hom.:

Cov.:

AF XY:

0.000881

AC XY:

AN XY:

73798

show subpopulations

Gnomad4 AFR

AF:

0.000268

Gnomad4 AMR

AF:

0.000724

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000585

Gnomad4 SAS

AF:

0.00399

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000785

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000551

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 29, 2024	This variant, c.348_374del, results in the deletion of 9 amino acid(s) of the THAP11 protein (p.Gln124_Gln132del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with THAP11-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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