Genetic Variant THAP4:p.Asp384Asn (chr2-241633007-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_015963.6(THAP4):c.1150G>A(p.Asp384Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000093 in 1,613,570 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 1 hom. )

Consequence

THAP4
NM_015963.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21663725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP4	NM_015963.6 link	c.1150G>A	p.Asp384Asn	missense_variant	Exon 2 of 6	ENST00000407315.6	NP_057047.4	Q8WY91-1
THAP4	XM_011511291.3 link	c.1222G>A	p.Asp408Asn	missense_variant	Exon 2 of 6		XP_011509593.1
THAP4	XM_005247016.5 link	c.1150G>A	p.Asp384Asn	missense_variant	Exon 2 of 6		XP_005247073.4
THAP4	XM_017004256.2 link	c.1222G>A	p.Asp408Asn	missense_variant	Exon 2 of 6		XP_016859745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP4	ENST00000407315.6 link	c.1150G>A	p.Asp384Asn	missense_variant	Exon 2 of 6	1	NM_015963.6	ENSP00000385006.1		Q8WY91-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000148

AC:

AN:

249378

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000589

Gnomad FIN exome

AF:

0.000470

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000821

AC:

120

AN:

1461312

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.000697

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000197

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000215

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1150G>A (p.D384N) alteration is located in exon 2 (coding exon 2) of the THAP4 gene. This alteration results from a G to A substitution at nucleotide position 1150, causing the aspartic acid (D) at amino acid position 384 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

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.075

T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.22

T;T

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.64

N;.

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.020

D;D

Polyphen

1.0

D;.

Vest4

0.57

MVP

0.94

MPC

1.3

ClinPred

0.17

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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