chr8-22249223-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001722.3(POLR3D):c.835C>T(p.Pro279Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
POLR3D
NM_001722.3 missense
NM_001722.3 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 7.65
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLR3D | NM_001722.3 | c.835C>T | p.Pro279Ser | missense_variant | 7/9 | ENST00000306433.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLR3D | ENST00000306433.9 | c.835C>T | p.Pro279Ser | missense_variant | 7/9 | 1 | NM_001722.3 | P1 | |
POLR3D | ENST00000397802.8 | c.835C>T | p.Pro279Ser | missense_variant | 6/8 | 1 | P1 | ||
POLR3D | ENST00000517789.2 | n.670C>T | non_coding_transcript_exon_variant | 5/6 | 5 | ||||
POLR3D | ENST00000518039.1 | c.*158+574C>T | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461864Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727234
GnomAD4 exome
AF:
AC:
8
AN:
1461864
Hom.:
Cov.:
33
AF XY:
AC XY:
5
AN XY:
727234
Gnomad4 AFR exome
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Gnomad4 SAS exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 26, 2022 | The c.835C>T (p.P279S) alteration is located in exon 7 (coding exon 6) of the POLR3D gene. This alteration results from a C to T substitution at nucleotide position 835, causing the proline (P) at amino acid position 279 to be replaced by a serine (S). 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of catalytic residue at P279 (P = 0.0011);Loss of catalytic residue at P279 (P = 0.0011);
MVP
MPC
0.82
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at