Variant chr12-71676834-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031435.4(THAP2):c.413T>A(p.Ile138Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,534 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

THAP2
NM_031435.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Variant links:

Genes affected

THAP2 (HGNC:20854): (THAP domain containing 2) Predicted to enable DNA binding activity and metal ion binding activity. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

THAP2 links:

LOC124902965 (HGNC:):

LOC124902965 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP2	NM_031435.4 linkuse as main transcript	c.413T>A	p.Ile138Asn	missense_variant	3/3	ENST00000308086.3
LOC124902965	XR_007063367.1 linkuse as main transcript	n.144-5052A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
THAP2	ENST00000308086.3 linkuse as main transcript	c.413T>A	p.Ile138Asn	missense_variant	3/3	1	NM_031435.4	P1
THAP2	ENST00000551488.5 linkuse as main transcript	c.197T>A	p.Ile66Asn	missense_variant	3/3	3
THAP2	ENST00000551238.1 linkuse as main transcript	c.197T>A	p.Ile66Asn	missense_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250908

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461396

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.413T>A (p.I138N) alteration is located in exon 3 (coding exon 3) of the THAP2 gene. This alteration results from a T to A substitution at nucleotide position 413, causing the isoleucine (I) at amino acid position 138 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Benign

0.94

DEOGEN2

Benign

0.10

T;T;.

Eigen

Benign

0.045

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.82

T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Uncertain

0.34

MutationAssessor

Benign

0.55

N;.;.

MutationTaster

Benign

0.87

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.91

P;.;.

Vest4

0.59

MutPred

0.48

Loss of stability (P = 0.0307);.;.;

MVP

0.92

MPC

0.76

ClinPred

0.93

GERP RS

4.9

Varity_R

0.62

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over