chr12-71674387-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031435.4(THAP2):ā€‹c.256A>Gā€‹(p.Ile86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000859 in 1,605,856 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000099 ( 0 hom., cov: 32)
Exomes š‘“: 0.000085 ( 1 hom. )

Consequence

THAP2
NM_031435.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.708
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.11972669).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THAP2NM_031435.4 linkuse as main transcriptc.256A>G p.Ile86Val missense_variant 2/3 ENST00000308086.3
LOC124902965XR_007063367.1 linkuse as main transcriptn.144-2605T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
THAP2ENST00000308086.3 linkuse as main transcriptc.256A>G p.Ile86Val missense_variant 2/31 NM_031435.4 P1
THAP2ENST00000551488.5 linkuse as main transcriptc.40A>G p.Ile14Val missense_variant 2/33
THAP2ENST00000551238.1 linkuse as main transcriptc.40A>G p.Ile14Val missense_variant 2/33

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152074
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000121
AC:
30
AN:
247888
Hom.:
0
AF XY:
0.000142
AC XY:
19
AN XY:
134054
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000209
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000665
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000178
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000846
AC:
123
AN:
1453782
Hom.:
1
Cov.:
33
AF XY:
0.0000899
AC XY:
65
AN XY:
722684
show subpopulations
Gnomad4 AFR exome
AF:
0.000121
Gnomad4 AMR exome
AF:
0.000183
Gnomad4 ASJ exome
AF:
0.000116
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000351
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000768
Gnomad4 OTH exome
AF:
0.000167
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152074
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000115
Hom.:
1
Bravo
AF:
0.0000945
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000115
AC:
14

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 26, 2022The c.256A>G (p.I86V) alteration is located in exon 2 (coding exon 2) of the THAP2 gene. This alteration results from a A to G substitution at nucleotide position 256, causing the isoleucine (I) at amino acid position 86 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
0.072
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
19
DANN
Benign
0.92
DEOGEN2
Benign
0.0041
T;T;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.090
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.67
T;T;T
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Uncertain
-0.00060
T
MutationAssessor
Benign
0.0
N;.;.
MutationTaster
Benign
0.99
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.050
N;N;N
REVEL
Uncertain
0.29
Sift
Benign
0.38
T;D;D
Sift4G
Benign
0.83
T;T;T
Polyphen
0.017
B;.;.
Vest4
0.22
MVP
0.57
MPC
0.11
ClinPred
0.022
T
GERP RS
3.9
Varity_R
0.028
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs147151987; hg19: chr12-72068167; API