chr16-67842866-G-GCAGCAGCAA

Position:

• chr16-67842866-G-GCAGCAGCAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_020457.3(THAP11):​c.321_329dupACAGCAGCA​(p.Gln108_Gln110dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 150,988 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (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: 1.10

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 16-67842866-G-GCAGCAGCAA is Benign according to our data. Variant chr16-67842866-G-GCAGCAGCAA is described in ClinVar as [Likely_benign]. Clinvar id is 2065673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP11	NM_020457.3	c.321_329dupACAGCAGCA	p.Gln108_Gln110dup	disruptive_inframe_insertion	1/1	ENST00000303596.3	NP_065190.2
CENPT	NM_025082.4	c.-492+4526_-492+4534dupTTGCTGCTG		intron_variant		ENST00000562787.6	NP_079358.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP11	ENST00000303596.3	c.321_329dupACAGCAGCA	p.Gln108_Gln110dup	disruptive_inframe_insertion	1/1	6	NM_020457.3	ENSP00000304689.1
CENPT	ENST00000562787.6	c.-492+4526_-492+4534dupTTGCTGCTG		intron_variant		2	NM_025082.4	ENSP00000457810.1

Frequencies

GnomAD3 genomes AF: 0.000172 AC: 26 AN: 150882 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000629

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000193

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000226 AC: 54 AN: 239300 Hom.: 0 AF XY: 0.000259 AC XY: 34 AN XY: 131332

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00236

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000991

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.000508

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000236 AC: 344 AN: 1456756 Hom.: 1 Cov.: 31 AF XY: 0.000248 AC XY: 180 AN XY: 724808

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00207

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000205

Gnomad4 OTH exome AF: 0.000515

GnomAD4 genome AF: 0.000172 AC: 26 AN: 150988 Hom.: 0 Cov.: 32 AF XY: 0.000257 AC XY: 19 AN XY: 73804

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000630

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000193

Gnomad4 OTH AF: 0.00

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

Jul 12, 2022

- -

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: rs757955307; hg19: chr16-67876769;