chr1-6625240-C-T

Variant names:

• chr1-6625240-C-T
• rs753064234
• NM_001195753.2:c.22C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001195753.2(THAP3):​c.22C>T​(p.Arg8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,545,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: THAP3 NM_001195753.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.786

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.22C>T	p.Arg8Trp	missense	Exon 2 of 6	NP_001182682.1	Q8WTV1-1
	THAP3	NM_001394496.1		c.22C>T	p.Arg8Trp	missense	Exon 1 of 5	NP_001381425.1
	THAP3	NM_001195752.2		c.22C>T	p.Arg8Trp	missense	Exon 2 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.22C>T	p.Arg8Trp	missense	Exon 2 of 6	ENSP00000054650.4	Q8WTV1-1
	THAP3	ENST00000922199.1		c.22C>T	p.Arg8Trp	missense	Exon 1 of 5	ENSP00000592258.1
	THAP3	ENST00000866305.1		c.22C>T	p.Arg8Trp	missense	Exon 1 of 5	ENSP00000536364.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000713 AC: 1 AN: 140350 AF XY: 0.0000130

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000194

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000172 AC: 24 AN: 1393136 Hom.: 0 Cov.: 33 AF XY: 0.0000204 AC XY: 14 AN XY: 687838

African (AFR) AF: 0.00 AC: 0 AN: 30366

American (AMR) AF: 0.00 AC: 0 AN: 35782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24894

East Asian (EAS) AF: 0.00 AC: 0 AN: 35144

South Asian (SAS) AF: 0.00 AC: 0 AN: 78780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4438

European-Non Finnish (NFE) AF: 0.0000222 AC: 24 AN: 1079144

Other (OTH) AF: 0.00 AC: 0 AN: 57716

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000189

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	0.46
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.068	N
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.94	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	1.8	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.69
Sift	Uncertain	0.025	D
Sift4G	Benign	0.19	T
Polyphen		0.99	D
Vest4		0.43
MutPred		0.54		Loss of disorder (P = 0)
MVP		0.98
MPC		1.1
ClinPred		0.92	D
GERP RS		3.7
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.61
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs753064234; hg19: chr1-6685300;