Variant 2-241633195-C-T 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_015963.6(THAP4):c.962G>A(p.Ser321Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

THAP4
NM_015963.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

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:

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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=0.18976164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
THAP4	NM_015963.6 linkuse as main transcript	c.962G>A	p.Ser321Asn	missense_variant	2/6	ENST00000407315.6	NP_057047.4
THAP4	XM_011511291.3 linkuse as main transcript	c.1034G>A	p.Ser345Asn	missense_variant	2/6		XP_011509593.1
THAP4	XM_005247016.5 linkuse as main transcript	c.962G>A	p.Ser321Asn	missense_variant	2/6		XP_005247073.4
THAP4	XM_017004256.2 linkuse as main transcript	c.1034G>A	p.Ser345Asn	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.962G>A	p.Ser321Asn	missense_variant	2/6	1	NM_015963.6	ENSP00000385006	P1	Q8WY91-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456430

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723792

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

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

Sep 06, 2022

The c.962G>A (p.S321N) 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 962, causing the serine (S) at amino acid position 321 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

0.14

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.19

MetaSVM

Uncertain

-0.033

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.15

REVEL

Benign

0.23

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.012

Polyphen

0.50

Vest4

0.20

MutPred

0.086

Loss of phosphorylation at S321 (P = 0.029);

MVP

0.83

MPC

0.78

ClinPred

0.29

GERP RS

2.4

Varity_R

0.055

gMVP

0.26

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