Variant rs1055171 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006466.4(POLR3F):c.840A>G(p.Thr280Thr) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.23

Variant links:

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]

POLR3F links:

POLR3F (HGNC:):

POLR3F links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
POLR3F	NM_006466.4 linkuse as main transcript	c.840A>G	p.Thr280Thr	synonymous_variant	8/9	ENST00000377603.5	NP_006457.2	Q9H1D9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR3F	ENST00000377603.5 linkuse as main transcript	c.840A>G	p.Thr280Thr	synonymous_variant	8/9	1	NM_006466.4	ENSP00000366828.4		Q9H1D9

Frequencies

GnomAD3 genomes

AF:

0.827

AC:

125648

AN:

151896

Hom.:

52238

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.870

AC XY:

632438

AN XY:

726892

show subpopulations

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.:

AF XY:

0.827

AC XY:

61403

AN XY:

74288

show subpopulations

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

LINK: link

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

Labcorp Genetics (formerly Invitae), Labcorp

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over