1-6625240-C-G

Variant names:

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

Variant summary

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

The NM_001195753.2(THAP3):​c.22C>G​(p.Arg8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,136 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: THAP3 NM_001195753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>G	p.Arg8Gly	missense	Exon 2 of 6	NP_001182682.1	Q8WTV1-1
	THAP3	NM_001394496.1		c.22C>G	p.Arg8Gly	missense	Exon 1 of 5	NP_001381425.1
	THAP3	NM_001195752.2		c.22C>G	p.Arg8Gly	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>G	p.Arg8Gly	missense	Exon 2 of 6	ENSP00000054650.4	Q8WTV1-1
	THAP3	ENST00000922199.1		c.22C>G	p.Arg8Gly	missense	Exon 1 of 5	ENSP00000592258.1
	THAP3	ENST00000866305.1		c.22C>G	p.Arg8Gly	missense	Exon 1 of 5	ENSP00000536364.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393136 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 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: 0.0000127 AC: 1 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: 0.00 AC: 0 AN: 1079144

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	1.0	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.54
Sift	Benign	0.26	T
Sift4G	Benign	0.33	T
Polyphen		0.32	B
Vest4		0.42
MutPred		0.44		Loss of MoRF binding (P = 0.0102)
MVP		0.93
MPC		0.90
ClinPred		0.91	D
GERP RS		3.7
PromoterAI		-0.0076	Neutral
Varity_R		0.41
gMVP		0.66
Mutation Taster		=83/17	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;