Genetic Variant THAP12:p.Asp266Asn (chr11-76352354-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004705.4(THAP12):c.796G>A(p.Asp266Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,459,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

THAP12
NM_004705.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

Variant links:

Genes affected

THAP12 (HGNC:9440): (THAP domain containing 12) Predicted to enable DNA binding activity; metal ion binding activity; and protein dimerization activity. Predicted to be involved in negative regulation of cell population proliferation and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

THAP12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.275282).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP12	NM_004705.4 link	c.796G>A	p.Asp266Asn	missense_variant	Exon 5 of 5	ENST00000260045.8	NP_004696.2	O43422-1A0A140VJQ7
THAP12	NR_130898.2 link	n.1187G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP12	ENST00000260045.8 link	c.796G>A	p.Asp266Asn	missense_variant	Exon 5 of 5	1	NM_004705.4	ENSP00000260045.3		O43422-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250348

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1459656

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.796G>A (p.D266N) alteration is located in exon 5 (coding exon 5) of the THAP12 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the aspartic acid (D) at amino acid position 266 to be replaced by an asparagine (N). 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

0.093

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.023

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.60

M_CAP

Benign

0.0050

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.14

Sift

Benign

0.14

Sift4G

Benign

0.14

Polyphen

0.57

Vest4

0.28

MutPred

0.60

Loss of loop (P = 0.2237);

MVP

0.17

MPC

1.4

ClinPred

0.47

GERP RS

5.0

Varity_R

0.11

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over