7-108564670-A-C

Position:

• chr7-108564670-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130475.3(THAP5):​c.709T>G​(p.Phe237Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: THAP5 NM_001130475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.865

Genes affected

THAP5 (HGNC:23188): (THAP domain containing 5) Enables protease binding activity. Involved in negative regulation of cell cycle and negative regulation of transcription by RNA polymerase II. Located in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

THAP5 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04051289).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP5	NM_001130475.3	c.709T>G	p.Phe237Val	missense_variant	3/3	ENST00000415914.4	NP_001123947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP5	ENST00000415914.4	c.709T>G	p.Phe237Val	missense_variant	3/3	1	NM_001130475.3	ENSP00000400500.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

The c.709T>G (p.F237V) alteration is located in exon 3 (coding exon 3) of the THAP5 gene. This alteration results from a T to G substitution at nucleotide position 709, causing the phenylalanine (F) at amino acid position 237 to be replaced by a valine (V). 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	0.053
BayesDel_addAF	Benign	0.00061	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	0.54
DANN	Benign	0.69
DEOGEN2	Benign	0.0093	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.48	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.041	T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.9	M;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.60	N;N
REVEL	Benign	0.20
Sift	Benign	0.80	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0010	B;.
Vest4		0.026
MutPred		0.12		Gain of glycosylation at T238 (P = 0.0945);.;
MVP		0.14
MPC		0.11
ClinPred		0.050	T
GERP RS		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs756074377; hg19: chr7-108205114;