16-67842862-G-GGCAGCAGCAGCAACAGCA

Position:

• chr16-67842862-G-GGCAGCAGCAGCAACAGCA

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_020457.3(THAP11):​c.330_347dupGCAGCAGCAACAGCAGCA​(p.Gln111_Gln116dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000603 in 150,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000093 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: THAP11 NM_020457.3 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40

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]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_020457.3
• BP6: Variant 16-67842862-G-GGCAGCAGCAGCAACAGCA is Benign according to our data. Variant chr16-67842862-G-GGCAGCAGCAGCAACAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 1635911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP11	NM_020457.3	c.330_347dupGCAGCAGCAACAGCAGCA	p.Gln111_Gln116dup	disruptive_inframe_insertion	1/1	ENST00000303596.3	NP_065190.2
CENPT	NM_025082.4	c.-492+4521_-492+4538dupTGCTGTTGCTGCTGCTGC		intron_variant		ENST00000562787.6	NP_079358.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP11	ENST00000303596.3	c.330_347dupGCAGCAGCAACAGCAGCA	p.Gln111_Gln116dup	disruptive_inframe_insertion	1/1	6	NM_020457.3	ENSP00000304689.1
CENPT	ENST00000562787.6	c.-492+4521_-492+4538dupTGCTGTTGCTGCTGCTGC		intron_variant		2	NM_025082.4	ENSP00000457810.1

Frequencies

GnomAD3 genomes AF: 0.000603 AC: 91 AN: 150838 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00216

Gnomad SAS AF: 0.000422

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.000483

GnomAD3 exomes AF: 0.000192 AC: 46 AN: 239172 Hom.: 0 AF XY: 0.000183 AC XY: 24 AN XY: 131384

Gnomad AFR exome AF: 0.000927

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00142

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000188

Gnomad OTH exome AF: 0.000340

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000927 AC: 135 AN: 1457032 Hom.: 1 Cov.: 31 AF XY: 0.0000979 AC XY: 71 AN XY: 724866

Gnomad4 AFR exome AF: 0.000928

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00104

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000306

Gnomad4 OTH exome AF: 0.000183

GnomAD4 genome AF: 0.000603 AC: 91 AN: 150958 Hom.: 0 Cov.: 32 AF XY: 0.000610 AC XY: 45 AN XY: 73762

Gnomad4 AFR AF: 0.00165

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00217

Gnomad4 SAS AF: 0.000423

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.000478

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs752755017; hg19: chr16-67876765;