16-67842866-GCAGCAGCAA-G

Position:

• chr16-67842866-GCAGCAGCAA-G

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_329delACAGCAGCA​(p.Gln108_Gln110del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000123 in 1,607,758 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: THAP11 NM_020457.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.87

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 16-67842866-GCAGCAGCAA-G is Benign according to our data. Variant chr16-67842866-GCAGCAGCAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 2200643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP11	NM_020457.3	c.321_329delACAGCAGCA	p.Gln108_Gln110del	disruptive_inframe_deletion	1/1	ENST00000303596.3	NP_065190.2
CENPT	NM_025082.4	c.-492+4526_-492+4534delTTGCTGCTG		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_329delACAGCAGCA	p.Gln108_Gln110del	disruptive_inframe_deletion	1/1	6	NM_020457.3	ENSP00000304689.1
CENPT	ENST00000562787.6	c.-492+4526_-492+4534delTTGCTGCTG		intron_variant		2	NM_025082.4	ENSP00000457810.1

Frequencies

GnomAD3 genomes AF: 0.000186 AC: 28 AN: 150882 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00189

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.000483

GnomAD3 exomes AF: 0.000213 AC: 51 AN: 239300 Hom.: 0 AF XY: 0.000175 AC XY: 23 AN XY: 131332

Gnomad AFR exome AF: 0.000142

Gnomad AMR exome AF: 0.000468

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000859

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000658

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000116 AC: 169 AN: 1456770 Hom.: 1 AF XY: 0.000119 AC XY: 86 AN XY: 724818

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000359

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.000975

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.0000496

Gnomad4 OTH exome AF: 0.0000998

GnomAD4 genome AF: 0.000185 AC: 28 AN: 150988 Hom.: 0 Cov.: 32 AF XY: 0.000244 AC XY: 18 AN XY: 73804

Gnomad4 AFR AF: 0.000268

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00189

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.0000712 Hom.: 0

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

Aug 23, 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;