Variant 2-241606395-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015963.6(THAP4):c.1319G>C(p.Gly440Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000275 in 1,600,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

THAP4
NM_015963.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP4	NM_015963.6 linkuse as main transcript	c.1319G>C	p.Gly440Ala	missense_variant	3/6	ENST00000407315.6	NP_057047.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP4	ENST00000407315.6 linkuse as main transcript	c.1319G>C	p.Gly440Ala	missense_variant	3/6	1	NM_015963.6	ENSP00000385006	P1	Q8WY91-1
THAP4	ENST00000402136.5 linkuse as main transcript	c.83G>C	p.Gly28Ala	missense_variant	2/5	1		ENSP00000385931		Q8WY91-2
THAP4	ENST00000402545.5 linkuse as main transcript	c.83G>C	p.Gly28Ala	missense_variant	2/5	5		ENSP00000384352

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

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:

0.0000617

AC:

AN:

226928

Hom.:

AF XY:

0.0000570

AC XY:

AN XY:

122742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000619

Gnomad ASJ exome

AF:

0.000737

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000395

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1448946

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

719546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000932

Gnomad4 ASJ exome

AF:

0.000814

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

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:

0.000113

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000578

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 25, 2022

The c.1319G>C (p.G440A) alteration is located in exon 3 (coding exon 3) of the THAP4 gene. This alteration results from a G to C substitution at nucleotide position 1319, causing the glycine (G) at amino acid position 440 to be replaced by an alanine (A). 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

Uncertain

0.44

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

.;T;T;.

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.2

.;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-5.6

D;N;D;.

REVEL

Pathogenic

0.71

Sift

Uncertain

0.014

D;T;D;.

Sift4G

Uncertain

0.030

D;T;D;D

Polyphen

0.99

D;D;.;.

Vest4

0.61

MutPred

0.73

.;Loss of disorder (P = 0.1398);.;.;

MVP

0.95

MPC

1.4

ClinPred

0.72

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.86

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