chr8-22245559-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001722.3(POLR3D):āc.110C>Gā(p.Pro37Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000206 in 1,262,346 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 (ā ).
Frequency
Genomes: š 0.00012 ( 0 hom., cov: 32)
Exomes š: 0.0000072 ( 0 hom. )
Consequence
POLR3D
NM_001722.3 missense
NM_001722.3 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 6.94
Genes affected
POLR3D (HGNC:1080): (RNA polymerase III subunit D) This gene complements a temperature-sensitive mutant isolated from the BHK-21 Syrian hamster cell line. It leads to a block in progression through the G1 phase of the cell cycle at nonpermissive temperatures. [provided by RefSeq, Jul 2008]
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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=0.07933149).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLR3D | NM_001722.3 | c.110C>G | p.Pro37Arg | missense_variant | 2/9 | ENST00000306433.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLR3D | ENST00000306433.9 | c.110C>G | p.Pro37Arg | missense_variant | 2/9 | 1 | NM_001722.3 | P1 | |
POLR3D | ENST00000397802.8 | c.110C>G | p.Pro37Arg | missense_variant | 1/8 | 1 | P1 | ||
POLR3D | ENST00000519237.5 | c.110C>G | p.Pro37Arg | missense_variant | 2/6 | 3 | |||
POLR3D | ENST00000518039.1 | c.110C>G | p.Pro37Arg | missense_variant, NMD_transcript_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000605 AC: 2AN: 33080Hom.: 0 AF XY: 0.0000559 AC XY: 1AN XY: 17880
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GnomAD4 exome AF: 0.00000721 AC: 8AN: 1110026Hom.: 0 Cov.: 31 AF XY: 0.00000571 AC XY: 3AN XY: 525768
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74490
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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 | May 09, 2023 | The c.110C>G (p.P37R) alteration is located in exon 2 (coding exon 1) of the POLR3D gene. This alteration results from a C to G substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 to be replaced by an arginine (R). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
B;.;B
Vest4
MutPred
Gain of MoRF binding (P = 4e-04);Gain of MoRF binding (P = 4e-04);Gain of MoRF binding (P = 4e-04);
MVP
MPC
0.40
ClinPred
T
GERP RS
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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