8-42838315-G-C

Variant names:

• chr8-42838315-G-C
• NM_018105.3:c.289C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_018105.3(THAP1):​c.289C>G​(p.Gln97Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: THAP1 NM_018105.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

Genes affected

THAP1 (HGNC:20856): (THAP domain containing 1) The protein encoded by this gene contains a THAP domain, a conserved DNA-binding domain. This protein colocalizes with the apoptosis response protein PAWR/PAR-4 in promyelocytic leukemia (PML) nuclear bodies, and functions as a proapoptotic factor that links PAWR to PML nuclear bodies. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a chain THAP domain-containing protein 1 (size 212) in uniprot entity THAP1_HUMAN there are 55 pathogenic changes around while only 2 benign (96%) in NM_018105.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044947326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP1	NM_018105.3	c.289C>G	p.Gln97Glu	missense_variant	Exon 3 of 3	ENST00000254250.7	NP_060575.1
THAP1	NM_199003.2	c.93C>G	p.His31Gln	missense_variant	Exon 2 of 2		NP_945354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP1	ENST00000254250.7	c.289C>G	p.Gln97Glu	missense_variant	Exon 3 of 3	1	NM_018105.3	ENSP00000254250.3
THAP1	ENST00000345117.2	c.93C>G	p.His31Gln	missense_variant	Exon 2 of 2	1		ENSP00000344966.2
THAP1	ENST00000529779.1	c.268-84C>G		intron_variant	Intron 2 of 2	5		ENSP00000433912.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461632 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	11
DANN	Benign	0.88
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.32	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.25
Sift	Benign	0.49	T
Sift4G	Benign	0.55	T
Vest4		0.12
MutPred		0.094		Gain of MoRF binding (P = 0.1218);
MVP		0.59
ClinPred		0.67	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-42693458;