16-67842450-G-A

Position:

• chr16-67842450-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020457.3(THAP11):​c.-105G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 886,710 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (214 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (105 hom.)
• Consequence: THAP11 NM_020457.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.564

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-67842450-G-A is Benign according to our data. Variant chr16-67842450-G-A is described in ClinVar as [Benign]. Clinvar id is 1234484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP11	NM_020457.3	c.-105G>A		5_prime_UTR_variant	1/1	ENST00000303596.3	NP_065190.2
CENPT	NM_025082.4	c.-492+4951C>T		intron_variant		ENST00000562787.6	NP_079358.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP11	ENST00000303596	c.-105G>A		5_prime_UTR_variant	1/1		NM_020457.3	ENSP00000304689.1
CENPT	ENST00000562787.6	c.-492+4951C>T		intron_variant		2	NM_025082.4	ENSP00000457810.1

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4866 AN: 150664 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00520

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00137

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.00415

Gnomad OTH AF: 0.0279

GnomAD4 exome AF: 0.00658 AC: 4843 AN: 735938 Hom.: 105 Cov.: 10 AF XY: 0.00631 AC XY: 2253 AN XY: 356838

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.00715

Gnomad4 EAS exome AF: 0.0000464

Gnomad4 SAS exome AF: 0.000591

Gnomad4 FIN exome AF: 0.00256

Gnomad4 NFE exome AF: 0.00400

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0324 AC: 4878 AN: 150772 Hom.: 214 Cov.: 32 AF XY: 0.0311 AC XY: 2290 AN XY: 73684

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.00520

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00137

Gnomad4 NFE AF: 0.00416

Gnomad4 OTH AF: 0.0272

Alfa AF: 0.000898 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7185408; hg19: chr16-67876353;