NM_152658.3:c.805A>G

Variant names:

• chr19-36035460-T-C
• rs140352604
• NM_152658.3:c.805A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152658.3(THAP8):​c.805A>G​(p.Thr269Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 1,613,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: THAP8 NM_152658.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0360
• Publications: 5 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11554697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP8	NM_152658.3	c.805A>G	p.Thr269Ala	missense_variant	Exon 4 of 4	ENST00000292894.2	NP_689871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP8	ENST00000292894.2	c.805A>G	p.Thr269Ala	missense_variant	Exon 4 of 4	1	NM_152658.3	ENSP00000292894.1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152154 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000160 AC: 40 AN: 250416 AF XY: 0.000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000319

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000282 AC: 412 AN: 1461628 Hom.: 0 Cov.: 31 AF XY: 0.000279 AC XY: 203 AN XY: 727120

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000134 AC: 6 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.000350 AC: 389 AN: 1111856

Other (OTH) AF: 0.000232 AC: 14 AN: 60376

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152154 Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16 AN XY: 74310

African (AFR) AF: 0.0000483 AC: 2 AN: 41428

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000391 Hom.: 0

Bravo AF: 0.000178

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.000600

EpiControl AF: 0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.805A>G (p.T269A) alteration is located in exon 4 (coding exon 4) of the THAP8 gene. This alteration results from a A to G substitution at nucleotide position 805, causing the threonine (T) at amino acid position 269 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.036
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.029	D
Polyphen		0.98	D
Vest4		0.078
MVP		0.87
MPC		0.098
ClinPred		0.070	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.060
gMVP		0.21
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: rs140352604; hg19: chr19-36526362;