Variant 2-241633096-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000407315.6(THAP4):c.1061A>C(p.Gln354Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

THAP4
ENST00000407315.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

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=0.20383748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP4	NM_015963.6 linkuse as main transcript	c.1061A>C	p.Gln354Pro	missense_variant	2/6	ENST00000407315.6	NP_057047.4	Q8WY91-1
THAP4	XM_011511291.3 linkuse as main transcript	c.1133A>C	p.Gln378Pro	missense_variant	2/6		XP_011509593.1
THAP4	XM_005247016.5 linkuse as main transcript	c.1061A>C	p.Gln354Pro	missense_variant	2/6		XP_005247073.4
THAP4	XM_017004256.2 linkuse as main transcript	c.1133A>C	p.Gln378Pro	missense_variant	2/6		XP_016859745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP4	ENST00000407315.6 linkuse as main transcript	c.1061A>C	p.Gln354Pro	missense_variant	2/6	1	NM_015963.6	ENSP00000385006.1		Q8WY91-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

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:

0.00

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:

0.00000798

AC:

AN:

250480

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461638

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

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:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000354

Hom.:

Bravo

AF:

0.00000378

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

Dec 21, 2023

The c.1061A>C (p.Q354P) alteration is located in exon 2 (coding exon 2) of the THAP4 gene. This alteration results from a A to C substitution at nucleotide position 1061, causing the glutamine (Q) at amino acid position 354 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

0.090

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.75

T;T

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.20

T;T

MetaSVM

Uncertain

0.17

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.030

N;.

REVEL

Benign

0.26

Sift

Benign

0.053

T;.

Sift4G

Benign

0.26

T;T

Polyphen

0.0020

B;.

Vest4

0.46

MVP

0.79

MPC

1.5

ClinPred

0.30

GERP RS

1.6

Varity_R

0.097

gMVP

0.63

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