NM_001195753.2:c.584C>T

Variant names:

• chr1-6632941-C-T
• NM_001195753.2:c.584C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195753.2(THAP3):​c.584C>T​(p.Thr195Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T195A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: THAP3 NM_001195753.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14
• Publications: 0 publications found

Genes affected

THAP3 (HGNC:20855): (THAP domain containing 3) Predicted to enable DNA binding activity and metal ion binding activity. Involved in positive regulation of transcription by RNA polymerase II. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2634543).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195753.2. 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
	THAP3	NM_001195753.2	MANE Select	c.584C>T	p.Thr195Ile	missense	Exon 6 of 6	NP_001182682.1	Q8WTV1-1
	THAP3	NM_001394496.1		c.605C>T	p.Thr202Ile	missense	Exon 5 of 5	NP_001381425.1
	THAP3	NM_001195752.2		c.581C>T	p.Thr194Ile	missense	Exon 6 of 6	NP_001182681.1	Q8WTV1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP3	ENST00000054650.9	TSL:1 MANE Select	c.584C>T	p.Thr195Ile	missense	Exon 6 of 6	ENSP00000054650.4	Q8WTV1-1
	THAP3	ENST00000922199.1		c.746C>T	p.Thr249Ile	missense	Exon 5 of 5	ENSP00000592258.1
	THAP3	ENST00000866305.1		c.605C>T	p.Thr202Ile	missense	Exon 5 of 5	ENSP00000536364.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460586 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726588

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52290

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.60	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.50
Sift	Benign	0.33	T
Sift4G	Benign	0.93	T
Polyphen		0.90	P
Vest4		0.19
MutPred		0.36		Loss of ubiquitination at K190 (P = 0.0313)
MVP		0.94
MPC		1.0
ClinPred		0.93	D
GERP RS		4.2
Varity_R		0.11
gMVP		0.32
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr1-6693001;