4-75521784-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_144721.6(THAP6):c.337G>A(p.Val113Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,613,056 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000061 ( 2 hom. )
Consequence
THAP6
NM_144721.6 missense
NM_144721.6 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 0.261
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.026251942).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THAP6 | NM_144721.6 | c.337G>A | p.Val113Ile | missense_variant | 4/5 | ENST00000311638.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THAP6 | ENST00000311638.7 | c.337G>A | p.Val113Ile | missense_variant | 4/5 | 1 | NM_144721.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151990Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000124 AC: 31AN: 250932Hom.: 1 AF XY: 0.000155 AC XY: 21AN XY: 135674
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GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461066Hom.: 2 Cov.: 32 AF XY: 0.0000839 AC XY: 61AN XY: 726854
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 151990Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74242
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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 13, 2022 | The c.337G>A (p.V113I) alteration is located in exon 4 (coding exon 3) of the THAP6 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the valine (V) at amino acid position 113 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;.;.;B
Vest4
MutPred
0.33
.;Gain of methylation at K111 (P = 0.1442);Gain of methylation at K111 (P = 0.1442);.;Gain of methylation at K111 (P = 0.1442);
MVP
MPC
0.15
ClinPred
T
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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