Variant 2-241606456-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015963.6(THAP4):c.1258C>T(p.Pro420Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000274 in 1,606,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

THAP4
NM_015963.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48

Variant links:

Genes affected

THAP4 (HGNC:23187): (THAP domain containing 4) Enables several functions, including heme binding activity; identical protein binding activity; and peroxynitrite isomerase activity. Involved in nitrate metabolic process and tyrosine metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

THAP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38008764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP4	NM_015963.6 link	c.1258C>T	p.Pro420Ser	missense_variant	3/6	ENST00000407315.6	NP_057047.4	Q8WY91-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THAP4	ENST00000407315.6 link	c.1258C>T	p.Pro420Ser	missense_variant	3/6	1	NM_015963.6	ENSP00000385006.1	Q8WY91-1
THAP4	ENST00000402136.5 link	c.22C>T	p.Pro8Ser	missense_variant	2/5	1		ENSP00000385931.1	Q8WY91-2
THAP4	ENST00000402545.5 link	c.22C>T	p.Pro8Ser	missense_variant	2/5	5		ENSP00000384352.1	B5MCC0

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000470

AC:

AN:

233972

Hom.:

AF XY:

0.0000474

AC XY:

AN XY:

126664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00104

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:

0.000175

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1454292

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

722742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000965

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000998

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000677

Hom.:

Bravo

AF:

0.0000604

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

Feb 03, 2022

The c.1258C>T (p.P420S) alteration is located in exon 3 (coding exon 3) of the THAP4 gene. This alteration results from a C to T substitution at nucleotide position 1258, causing the proline (P) at amino acid position 420 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

.;T;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Uncertain

0.54

MutationAssessor

Uncertain

2.2

.;M;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

D;D;D;.

REVEL

Pathogenic

0.74

Sift

Benign

0.047

D;D;D;.

Sift4G

Uncertain

0.022

D;D;D;D

Polyphen

0.60

P;D;.;.

Vest4

0.50

MutPred

0.75

.;Gain of phosphorylation at P420 (P = 0.0377);.;.;

MVP

0.96

MPC

1.4

ClinPred

0.64

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.64

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