rs1301209531

Variant names:

• chr1-6628632-C-A
• rs1301209531
• NM_001195753.2:c.208C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-6628632-C-A
• chr1-6628632-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001195753.2(THAP3):​c.208C>A​(p.Arg70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R70C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THAP3 NM_001195753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP3	NM_001195753.2	c.208C>A	p.Arg70Ser	missense_variant	Exon 3 of 6	ENST00000054650.9	NP_001182682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP3	ENST00000054650.9	c.208C>A	p.Arg70Ser	missense_variant	Exon 3 of 6	1	NM_001195753.2	ENSP00000054650.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Pathogenic	0.57	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Pathogenic	0.79
Sift	Benign	0.047	D;T;D
Sift4G	Benign	0.080	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.56
MutPred		0.56		Gain of ubiquitination at K71 (P = 0.0467);Gain of ubiquitination at K71 (P = 0.0467);Gain of ubiquitination at K71 (P = 0.0467);
MVP		0.94
MPC		1.2
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.71

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

Other links and lift over

dbSNP: rs1301209531; hg19: chr1-6688692;