rs1055171

chr20-18481777-A-Gchr20-18481777-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006466.4(POLR3F):c.840A>G(p.Thr280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,613,084 control chromosomes in the GnomAD database, including 603,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52257 hom., cov: 30)
  • Exomes 𝑓: 0.87 (551655 hom.)
• Consequence: POLR3F NM_006466.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23

Genes affected

POLR3F (HGNC:15763): (RNA polymerase III subunit F) The protein encoded by this gene is one of more than a dozen subunits forming eukaryotic RNA polymerase III (RNA Pol III), which transcribes 5S ribosomal RNA and tRNA genes. This protein has been shown to bind both TFIIIB90 and TBP, two subunits of RNA polymerase III transcription initiation factor IIIB (TFIIIB). Unlike most of the other RNA Pol III subunits, the encoded protein is unique to this polymerase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-18481777-A-G is Benign according to our data. Variant chr20-18481777-A-G is described in ClinVar as [Benign]. Clinvar id is 1995826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR3F	NM_006466.4	c.840A>G	p.Thr280=	synonymous_variant	8/9	ENST00000377603.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR3F	ENST00000377603.5	c.840A>G	p.Thr280=	synonymous_variant	8/9	1	NM_006466.4	P4

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125648 AN: 151896 Hom.: 52238 Cov.: 30

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.822

GnomAD3 exomes AF: 0.842 AC: 211571 AN: 251126 Hom.: 89593 AF XY: 0.851 AC XY: 115426 AN XY: 135680

Gnomad AFR exome AF: 0.747

Gnomad AMR exome AF: 0.738

Gnomad ASJ exome AF: 0.849

Gnomad EAS exome AF: 0.808

Gnomad SAS exome AF: 0.909

Gnomad FIN exome AF: 0.870

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.851

GnomAD4 exome AF: 0.868 AC: 1268195 AN: 1461070 Hom.: 551655 Cov.: 39 AF XY: 0.870 AC XY: 632438 AN XY: 726892

Gnomad4 AFR exome AF: 0.742

Gnomad4 AMR exome AF: 0.745

Gnomad4 ASJ exome AF: 0.844

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.908

Gnomad4 FIN exome AF: 0.870

Gnomad4 NFE exome AF: 0.876

Gnomad4 OTH exome AF: 0.862

GnomAD4 genome AF: 0.827 AC: 125703 AN: 152014 Hom.: 52257 Cov.: 30 AF XY: 0.827 AC XY: 61403 AN XY: 74288

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.824

Alfa AF: 0.854 Hom.: 70906

Bravo AF: 0.814

Asia WGS AF: 0.848 AC: 2950 AN: 3478

EpiCase AF: 0.864

EpiControl AF: 0.863

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 96% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.092
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1055171; hg19: chr20-18462421;