rs535124177

Variant names:

• chr19-36039343-G-A
• rs535124177
• NM_152658.3:c.652C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-36039343-G-A
• chr19-36039343-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152658.3(THAP8):​c.652C>T​(p.Arg218Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,522,678 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: THAP8 NM_152658.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042548776).
• BP6: Variant 19-36039343-G-A is Benign according to our data. Variant chr19-36039343-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2455764.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP8	NM_152658.3	c.652C>T	p.Arg218Cys	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.652C>T	p.Arg218Cys	missense_variant	Exon 3 of 4	1	NM_152658.3	ENSP00000292894.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152260 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00129 AC: 158 AN: 122250 AF XY: 0.00103

Gnomad AFR exome AF: 0.000162

Gnomad AMR exome AF: 0.00568

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000218

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000225 AC: 308 AN: 1370300 Hom.: 1 Cov.: 30 AF XY: 0.000225 AC XY: 152 AN XY: 675180

African (AFR) AF: 0.0000643 AC: 2 AN: 31098

American (AMR) AF: 0.00459 AC: 157 AN: 34180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24310

East Asian (EAS) AF: 0.00 AC: 0 AN: 35272

South Asian (SAS) AF: 0.000966 AC: 75 AN: 77648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4734

European-Non Finnish (NFE) AF: 0.0000616 AC: 66 AN: 1071938

Other (OTH) AF: 0.000140 AC: 8 AN: 57176

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152378 Hom.: 1 Cov.: 33 AF XY: 0.000228 AC XY: 17 AN XY: 74516

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.00118 AC: 18 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.000457

ExAC AF: 0.000491 AC: 43

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 28, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.055
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.086
Sift	Benign	0.17	T
Sift4G	Uncertain	0.019	D
Polyphen		0.0010	B
Vest4		0.11
MVP		0.23
MPC		0.082
ClinPred		0.018	T
GERP RS		-1.4
Varity_R		0.056
gMVP		0.055
Mutation Taster		=98/2	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: rs535124177; hg19: chr19-36530245; COSMIC: COSV53078086; COSMIC: COSV53078086;