chr8-22249124-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001722.3(POLR3D):c.736C>T(p.Pro246Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001722.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLR3D | NM_001722.3 | c.736C>T | p.Pro246Ser | missense_variant | 7/9 | ENST00000306433.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLR3D | ENST00000306433.9 | c.736C>T | p.Pro246Ser | missense_variant | 7/9 | 1 | NM_001722.3 | P1 | |
POLR3D | ENST00000397802.8 | c.736C>T | p.Pro246Ser | missense_variant | 6/8 | 1 | P1 | ||
POLR3D | ENST00000517789.2 | n.571C>T | non_coding_transcript_exon_variant | 5/6 | 5 | ||||
POLR3D | ENST00000518039.1 | c.*158+475C>T | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152004Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727236
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74224
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2023 | The c.736C>T (p.P246S) 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 736, causing the proline (P) at amino acid position 246 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at