12-71677079-C-G

Position:

• chr12-71677079-C-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.658C>G​(p.Leu220Val) 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: THAP2 NM_031435.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.613

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]

LOC124902965 (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=0.04747194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP2	NM_031435.4	c.658C>G	p.Leu220Val	missense_variant	3/3	ENST00000308086.3
LOC124902965	XR_007063367.1	n.144-5297G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THAP2	ENST00000308086.3	c.658C>G	p.Leu220Val	missense_variant	3/3	1	NM_031435.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 08, 2022

The c.658C>G (p.L220V) alteration is located in exon 3 (coding exon 3) of the THAP2 gene. This alteration results from a C to G substitution at nucleotide position 658, causing the leucine (L) at amino acid position 220 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	0.064
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.047	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.031
MutPred		0.24		Gain of methylation at K221 (P = 0.0321);
MVP		0.57
MPC		0.37
ClinPred		0.32	T
GERP RS		-0.89
Varity_R		0.13
gMVP		0.16

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: chr12-72070859;