rs1171096047

Variant names:

• chr19-36039327-C-A
• rs1171096047
• NM_152658.3:c.668G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-36039327-C-A
• chr19-36039327-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152658.3(THAP8):​c.668G>T​(p.Arg223Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,333,696 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. R223H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: THAP8 NM_152658.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046830446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP8	NM_152658.3	c.668G>T	p.Arg223Leu	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.668G>T	p.Arg223Leu	missense_variant	Exon 3 of 4	1	NM_152658.3	ENSP00000292894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333696 Hom.: 0 Cov.: 30 AF XY: 0.00000153 AC XY: 1 AN XY: 653672

African (AFR) AF: 0.00 AC: 0 AN: 29844

American (AMR) AF: 0.00 AC: 0 AN: 29054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21898

East Asian (EAS) AF: 0.00 AC: 0 AN: 34370

South Asian (SAS) AF: 0.00 AC: 0 AN: 71732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4166

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1054872

Other (OTH) AF: 0.00 AC: 0 AN: 55546

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.020
DANN	Benign	0.14
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.60
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.043
Sift	Benign	0.073	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0030	B
Vest4		0.13
MutPred		0.31		Loss of MoRF binding (P = 0.0185);
MVP		0.28
MPC		0.075
ClinPred		0.060	T
GERP RS		-4.5
Varity_R		0.063
gMVP		0.072
Mutation Taster		=96/4	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: rs1171096047; hg19: chr19-36530229;