4-82907800-T-C

Position:

• chr4-82907800-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024672.6(THAP9):​c.596T>C​(p.Leu199Ser) 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: 32)
• Consequence: THAP9 NM_024672.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.814

Genes affected

THAP9 (HGNC:23192): (THAP domain containing 9) Enables sequence-specific DNA binding activity and transposase activity. Involved in DNA integration and transposition, DNA-mediated. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07649511).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP9	NM_024672.6	c.596T>C	p.Leu199Ser	missense_variant	4/5	ENST00000302236.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THAP9	ENST00000302236.10	c.596T>C	p.Leu199Ser	missense_variant	4/5	1	NM_024672.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Aug 16, 2022

The c.596T>C (p.L199S) alteration is located in exon 4 (coding exon 4) of the THAP9 gene. This alteration results from a T to C substitution at nucleotide position 596, causing the leucine (L) at amino acid position 199 to be replaced by a serine (S). 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	0.095
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.045
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.014	B
Vest4		0.30
MutPred		0.46		Gain of disorder (P = 0.0172);
MVP		0.085
MPC		0.44
ClinPred		0.45	T
GERP RS		1.4
Varity_R		0.067
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-83828953;