chr19-36039609-C-A

Variant names:

• chr19-36039609-C-A
• rs1401926088
• NM_152658.3:c.386G>T

Variant summary

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

The NM_152658.3(THAP8):​c.386G>T​(p.Arg129Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,357,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. R129H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: THAP8 NM_152658.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 0 publications found

Genes affected

THAP8 (HGNC:23191): (THAP domain containing 8) Predicted to enable DNA binding activity and metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267698 (HGNC:):

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=0.08831403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP8	NM_152658.3	c.386G>T	p.Arg129Leu	missense_variant	Exon 3 of 4	ENST00000292894.2	NP_689871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP8	ENST00000292894.2	c.386G>T	p.Arg129Leu	missense_variant	Exon 3 of 4	1	NM_152658.3	ENSP00000292894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1357522 Hom.: 0 Cov.: 33 AF XY: 0.00000150 AC XY: 1 AN XY: 665288

African (AFR) AF: 0.00 AC: 0 AN: 30380

American (AMR) AF: 0.00 AC: 0 AN: 29340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22134

East Asian (EAS) AF: 0.00 AC: 0 AN: 35326

South Asian (SAS) AF: 0.00 AC: 0 AN: 72830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5432

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058060

Other (OTH) AF: 0.0000178 AC: 1 AN: 56124

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	5.7
DANN	Benign	0.77
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.22
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.20
Sift	Benign	0.041	D
Sift4G	Benign	0.22	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.38		Gain of sheet (P = 0.0085);
MVP		0.46
MPC		0.080
ClinPred		0.078	T
GERP RS		0.017
Varity_R		0.062
gMVP		0.21
Mutation Taster		=299/1	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: rs1401926088; hg19: chr19-36530511;