rs752755017

Variant names:

• chr16-67842862-GGCAGCAGCAGCAACAGCA-G
• rs752755017
• NM_020457.3:c.330_347delGCAGCAGCAACAGCAGCA

Your query was ambiguous. Multiple possible variants found:

• chr16-67842862-GGCAGCAGCAGCAACAGCA-G
• chr16-67842862-GGCAGCAGCAGCAACAGCA-GGCAGCAGCAGCAACAGCAGCAGCAGCAGCAACAGCA

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_020457.3(THAP11):​c.330_347delGCAGCAGCAACAGCAGCA​(p.Gln111_Gln116del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000344 in 150,964 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: THAP11 NM_020457.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.87
• 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: Likely_benign. The variant received -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_020457.3
• BP6: Variant 16-67842862-GGCAGCAGCAGCAACAGCA-G is Benign according to our data. Variant chr16-67842862-GGCAGCAGCAGCAACAGCA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2866512.Status of the report is criteria_provided_single_submitter, 1 stars.

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.330_347delGCAGCAGCAACAGCAGCA	p.Gln111_Gln116del	disruptive_inframe_deletion	Exon 1 of 1	NP_065190.2
	CENPT	NM_025082.4	MANE Select	c.-492+4521_-492+4538delTGCTGTTGCTGCTGCTGC		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.330_347delGCAGCAGCAACAGCAGCA	p.Gln111_Gln116del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000304689.1	Q96EK4
	CENPT	ENST00000562787.6	TSL:2 MANE Select	c.-492+4521_-492+4538delTGCTGTTGCTGCTGCTGC		intron	N/A	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000969291.1		c.-635+4700_-635+4717delTGCTGTTGCTGCTGCTGC		intron	N/A	ENSP00000639350.1

Frequencies

GnomAD3 genomes AF: 0.000345 AC: 52 AN: 150844 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000519

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.000334 AC: 80 AN: 239172 AF XY: 0.000282

Gnomad AFR exome AF: 0.000143

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000283

Gnomad FIN exome AF: 0.000143

Gnomad NFE exome AF: 0.000480

Gnomad OTH exome AF: 0.000510

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000414 AC: 603 AN: 1457058 Hom.: 0 AF XY: 0.000389 AC XY: 282 AN XY: 724880

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000210 AC: 7 AN: 33412

American (AMR) AF: 0.000336 AC: 15 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26072

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39430

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86160

European-Finnish (FIN) AF: 0.0000968 AC: 5 AN: 51650

Middle Eastern (MID) AF: 0.000539 AC: 3 AN: 5566

European-Non Finnish (NFE) AF: 0.000475 AC: 527 AN: 1110040

Other (OTH) AF: 0.000416 AC: 25 AN: 60114

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000344 AC: 52 AN: 150964 Hom.: 0 Cov.: 32 AF XY: 0.000298 AC XY: 22 AN XY: 73764

African (AFR) AF: 0.000267 AC: 11 AN: 41186

American (AMR) AF: 0.000132 AC: 2 AN: 15188

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

East Asian (EAS) AF: 0.000394 AC: 2 AN: 5072

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

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

European-Non Finnish (NFE) AF: 0.000519 AC: 35 AN: 67476

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

Alfa AF: 0.000144 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

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		4.9
Mutation Taster		=183/17	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs752755017; hg19: chr16-67876765;