chr2-241633007-C-T

Variant names:

• chr2-241633007-C-T
• rs762065419
• NM_015963.6:c.1150G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21663725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015963.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP4	NM_015963.6	MANE Select	c.1150G>A	p.Asp384Asn	missense	Exon 2 of 6	NP_057047.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP4	ENST00000407315.6	TSL:1 MANE Select	c.1150G>A	p.Asp384Asn	missense	Exon 2 of 6	ENSP00000385006.1	Q8WY91-1
	THAP4	ENST00000863246.1		c.1150G>A	p.Asp384Asn	missense	Exon 2 of 6	ENSP00000533305.1
	THAP4	ENST00000863245.1		c.1150G>A	p.Asp384Asn	missense	Exon 2 of 6	ENSP00000533304.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152258 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000148 AC: 37 AN: 249378 AF XY: 0.000163

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 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.: 1 Cov.: 30 AF XY: 0.000107 AC XY: 78 AN XY: 726932

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.0000895 AC: 4 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000580 AC: 50 AN: 86208

European-Finnish (FIN) AF: 0.000697 AC: 37 AN: 53088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111900

Other (OTH) AF: 0.0000994 AC: 6 AN: 60364

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74388

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.000850 AC: 13 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68046

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.000215

ExAC AF: 0.000148 AC: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.22	T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.64	N
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.57
MVP		0.94
MPC		1.3
ClinPred		0.17	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.84
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs762065419; hg19: chr2-242572422;