16-67842794-C-T

Variant names:

• chr16-67842794-C-T
• rs188675529
• NM_020457.3:c.240C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_020457.3(THAP11):​c.240C>T​(p.Phe80Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000588 in 1,611,282 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (10 hom.)
• Consequence: THAP11 NM_020457.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21
• Publications: 8 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 16-67842794-C-T is Benign according to our data. Variant chr16-67842794-C-T is described in ClinVar as Benign. ClinVar VariationId is 2046828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.21 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000814 (124/152310) while in subpopulation EAS AF = 0.0207 (107/5174). AF 95% confidence interval is 0.0175. There are 1 homozygotes in GnomAd4. There are 71 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

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.240C>T	p.Phe80Phe	synonymous	Exon 1 of 1	NP_065190.2
	CENPT	NM_025082.4	MANE Select	c.-492+4607G>A		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.240C>T	p.Phe80Phe	synonymous	Exon 1 of 1	ENSP00000304689.1	Q96EK4
	CENPT	ENST00000562787.6	TSL:2 MANE Select	c.-492+4607G>A		intron	N/A	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000969291.1		c.-635+4786G>A		intron	N/A	ENSP00000639350.1

Frequencies

GnomAD3 genomes AF: 0.000815 AC: 124 AN: 152194 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00161 AC: 391 AN: 242324 AF XY: 0.00148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0213

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000565 AC: 824 AN: 1458972 Hom.: 10 Cov.: 31 AF XY: 0.000533 AC XY: 387 AN XY: 725816

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.0000225 AC: 1 AN: 44466

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

East Asian (EAS) AF: 0.0187 AC: 739 AN: 39526

South Asian (SAS) AF: 0.000291 AC: 25 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52398

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5682

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111164

Other (OTH) AF: 0.000813 AC: 49 AN: 60234

GnomAD4 genome AF: 0.000814 AC: 124 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.000953 AC XY: 71 AN XY: 74484

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.000588 AC: 9 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0207 AC: 107 AN: 5174

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.000929

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		2.2
PromoterAI		0.14	Neutral
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs188675529; hg19: chr16-67876697; COSMIC: COSV54647157; COSMIC: COSV54647157;