chr1-6625234-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001195753.2(THAP3):c.16G>A(p.Ala6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,543,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
THAP3
NM_001195753.2 missense
NM_001195753.2 missense
Scores
7
7
5
Clinical Significance
Conservation
PhyloP100: 2.72
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.909
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THAP3 | NM_001195753.2 | c.16G>A | p.Ala6Thr | missense_variant | 2/6 | ENST00000054650.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THAP3 | ENST00000054650.9 | c.16G>A | p.Ala6Thr | missense_variant | 2/6 | 1 | NM_001195753.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000435 AC: 6AN: 137988Hom.: 0 AF XY: 0.0000663 AC XY: 5AN XY: 75406
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GnomAD4 exome AF: 0.0000115 AC: 16AN: 1391766Hom.: 0 Cov.: 33 AF XY: 0.0000102 AC XY: 7AN XY: 687066
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74414
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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 | Jan 19, 2022 | The c.16G>A (p.A6T) alteration is located in exon 2 (coding exon 1) of the THAP3 gene. This alteration results from a G to A substitution at nucleotide position 16, causing the alanine (A) at amino acid position 6 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;N;N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of phosphorylation at A6 (P = 0.0207);Gain of phosphorylation at A6 (P = 0.0207);Gain of phosphorylation at A6 (P = 0.0207);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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