16-67842572-C-T

Position:

chr16-67842572-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_020457.3(THAP11):c.18C>T(p.Cys6Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,537,622 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

THAP11
NM_020457.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.74

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 16-67842572-C-T is Benign according to our data. Variant chr16-67842572-C-T is described in ClinVar as [Benign]. Clinvar id is 1544891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.74 with no splicing effect.

BS2

High AC in GnomAd4 at 170 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP11	NM_020457.3 linkuse as main transcript	c.18C>T	p.Cys6Cys	synonymous_variant	1/1	ENST00000303596.3	NP_065190.2	Q96EK4
CENPT	NM_025082.4 linkuse as main transcript	c.-492+4829G>A		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.18C>T	p.Cys6Cys	synonymous_variant	1/1	6	NM_020457.3	ENSP00000304689.1		Q96EK4
CENPT	ENST00000562787.6 linkuse as main transcript	c.-492+4829G>A		intron_variant		2	NM_025082.4	ENSP00000457810.1		Q96BT3-1

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

170

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00105

AC:

155

AN:

147776

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

78244

show subpopulations

Gnomad AFR exome

AF:

0.000238

Gnomad AMR exome

AF:

0.000705

Gnomad ASJ exome

AF:

0.00100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000322

Gnomad FIN exome

AF:

0.000837

Gnomad NFE exome

AF:

0.00188

Gnomad OTH exome

AF:

0.000946

GnomAD4 exome

AF:

0.00165

AC:

2288

AN:

1385340

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1063

AN XY:

681386

show subpopulations

Gnomad4 AFR exome

AF:

0.000287

Gnomad4 AMR exome

AF:

0.000629

Gnomad4 ASJ exome

AF:

0.00106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000307

Gnomad4 FIN exome

AF:

0.000656

Gnomad4 NFE exome

AF:

0.00196

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00112

AC:

170

AN:

152282

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.00118

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 24, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 08, 2024

Variant summary: CENPT c.-492+4829G>A is located in the untranslated mRNA region upstream of the initiation codon. This variant corresponds to a synonymous variant in a different gene, i.e. THAP11 c.18C>T (p.Cys6=). Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0016 in 1530762 control chromosomes in the gnomAD database (v4.1 dataset), including 4 homozygotes. To our knowledge, no occurrence of c.-492+4829G>A in individuals affected with Short Stature and Microcephaly with Genital Anomalies and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1544891). Based on the evidence outlined above, the variant was classified as benign. -

THAP11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 04, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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