12-71677010-A-G

Position:

• chr12-71677010-A-G

Variant summary

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

The NM_031435.4(THAP2):​c.589A>G​(p.Ser197Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THAP2 NM_031435.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

Genes affected

THAP2 (HGNC:20854): (THAP domain containing 2) Predicted to enable DNA binding activity and metal ion binding activity. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258064 (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=0.05408773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP2	NM_031435.4	c.589A>G	p.Ser197Gly	missense_variant	3/3	ENST00000308086.3	NP_113623.1
LOC124902965	XR_007063367.1	n.144-5228T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP2	ENST00000308086.3	c.589A>G	p.Ser197Gly	missense_variant	3/3	1	NM_031435.4	ENSP00000310796.2
ENSG00000258064	ENST00000548802.1	n.195+2612A>G		intron_variant		3		ENSP00000454911.2
THAP2	ENST00000551488.5	c.*42A>G		downstream_gene_variant		3		ENSP00000448904.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Nov 15, 2024

The c.589A>G (p.S197G) alteration is located in exon 3 (coding exon 3) of the THAP2 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the serine (S) at amino acid position 197 to be replaced by a glycine (G). 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	0.073
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.054	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.18
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.056	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.22		Gain of glycosylation at S196 (P = 0.0351);
MVP		0.53
MPC		0.11
ClinPred		0.050	T
GERP RS		3.7
Varity_R		0.10
gMVP		0.060

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: chr12-72070790;