16-67842862-G-GGCA

Variant names:

• chr16-67842862-G-GGCA
• rs754326743
• NM_020457.3:c.318_320dupGCA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_020457.3(THAP11):​c.318_320dupGCA​(p.Gln107dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000815 in 1,608,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q107Q) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: THAP11 NM_020457.3 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• short stature and microcephaly with genital anomalies

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_020457.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020457.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP11	NM_020457.3	MANE Select	c.318_320dupGCA	p.Gln107dup	disruptive_inframe_insertion	Exon 1 of 1	NP_065190.2
	CENPT	NM_025082.4	MANE Select	c.-492+4536_-492+4538dupTGC		intron	N/A	NP_079358.3	Q96BT3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP11	ENST00000303596.3	TSL:6 MANE Select	c.318_320dupGCA	p.Gln107dup	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000304689.1	Q96EK4
	CENPT	ENST00000562787.6	TSL:2 MANE Select	c.-492+4536_-492+4538dupTGC		intron	N/A	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000969291.1		c.-635+4715_-635+4717dupTGC		intron	N/A	ENSP00000639350.1

Frequencies

GnomAD3 genomes AF: 0.0000994 AC: 15 AN: 150844 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000889

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.0000711 AC: 17 AN: 239172 AF XY: 0.0000685

Gnomad AFR exome AF: 0.000143

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000113

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000789 AC: 115 AN: 1457074 Hom.: 0 Cov.: 31 AF XY: 0.0000800 AC XY: 58 AN XY: 724884

African (AFR) AF: 0.000120 AC: 4 AN: 33412

American (AMR) AF: 0.0000224 AC: 1 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.0000761 AC: 3 AN: 39430

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5566

European-Non Finnish (NFE) AF: 0.0000901 AC: 100 AN: 1110052

Other (OTH) AF: 0.0000832 AC: 5 AN: 60114

GnomAD4 genome AF: 0.000106 AC: 16 AN: 150964 Hom.: 0 Cov.: 32 AF XY: 0.0000949 AC XY: 7 AN XY: 73764

African (AFR) AF: 0.0000971 AC: 4 AN: 41186

American (AMR) AF: 0.0000658 AC: 1 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5072

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000889 AC: 6 AN: 67476

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000869 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
Mutation Taster		=81/19	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs754326743; hg19: chr16-67876765;