1-6633018-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001195753.2(THAP3):c.661C>T(p.Arg221Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,612,072 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
THAP3
NM_001195753.2 missense
NM_001195753.2 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 1.32
Genes affected
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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=0.22999766).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THAP3 | NM_001195753.2 | c.661C>T | p.Arg221Cys | missense_variant | 6/6 | ENST00000054650.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THAP3 | ENST00000054650.9 | c.661C>T | p.Arg221Cys | missense_variant | 6/6 | 1 | NM_001195753.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152244Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000139 AC: 33AN: 237674Hom.: 0 AF XY: 0.000160 AC XY: 21AN XY: 130946
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GnomAD4 exome AF: 0.000134 AC: 196AN: 1459710Hom.: 1 Cov.: 30 AF XY: 0.000140 AC XY: 102AN XY: 726088
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152362Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74498
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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 submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | The c.661C>T (p.R221C) alteration is located in exon 6 (coding exon 5) of the THAP3 gene. This alteration results from a C to T substitution at nucleotide position 661, causing the arginine (R) at amino acid position 221 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at