Variant 12-71677053-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031435.4(THAP2):c.632A>C(p.Gln211Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

THAP2
NM_031435.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.793

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07864651).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP2	NM_031435.4 linkuse as main transcript	c.632A>C	p.Gln211Pro	missense_variant	3/3	ENST00000308086.3
LOC124902965	XR_007063367.1 linkuse as main transcript	n.144-5271T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THAP2	ENST00000308086.3 linkuse as main transcript	c.632A>C	p.Gln211Pro	missense_variant	3/3	1	NM_031435.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249684

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134968

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1460452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726492

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Cov.:

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

Jul 26, 2022

The c.632A>C (p.Q211P) alteration is located in exon 3 (coding exon 3) of the THAP2 gene. This alteration results from a A to C substitution at nucleotide position 632, causing the glutamine (Q) at amino acid position 211 to be replaced by a proline (P). 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

Benign

0.081

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.59

M_CAP

Benign

0.030

MetaRNN

Benign

0.079

MetaSVM

Uncertain

-0.078

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.74

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.32

REVEL

Uncertain

0.48

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.022

Polyphen

0.0010

Vest4

0.22

MutPred

0.14

Loss of helix (P = 0.0376);

MVP

0.67

MPC

0.15

ClinPred

0.14

GERP RS

3.3

Varity_R

0.11

gMVP

0.18

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