Genetic Variant POLR3F:c.-72C>A (chr20-18467435-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006466.4(POLR3F):c.-72C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 1,546,632 control chromosomes in the GnomAD database, including 703,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.91 ( 63424 hom., cov: 37)

Exomes 𝑓: 0.96 ( 640117 hom. )

Consequence

POLR3F
NM_006466.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.32

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:

DZANK1 (HGNC:15858): (double zinc ribbon and ankyrin repeat domains 1) This gene contains two ankyrin repeat-encoding regions. Ankyrin repeats are tandemly repeated modules of about 33 amino acids described as L-shaped structures consisting of a beta-hairpin and two alpha-helices. Ankyrin repeats occur in a large number of functionally diverse proteins, mainly from eukaryotes, and are known to function as protein-protein interaction domains. [provided by RefSeq, Dec 2018]

DZANK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 20-18467435-C-A is Benign according to our data. Variant chr20-18467435-C-A is described in ClinVar as [Benign]. Clinvar id is 2688249.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR3F	NM_006466.4 link	c.-72C>A		5_prime_UTR_variant	Exon 1 of 9	ENST00000377603.5	NP_006457.2	Q9H1D9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3F	ENST00000377603 link	c.-72C>A		5_prime_UTR_variant	Exon 1 of 9	1	NM_006466.4	ENSP00000366828.4		Q9H1D9

Frequencies

GnomAD3 genomes

AF:

0.908

AC:

138178

AN:

152220

Hom.:

63391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.901

Gnomad AMR

AF:

0.934

Gnomad ASJ

AF:

0.975

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.914

Gnomad FIN

AF:

0.974

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.967

Gnomad OTH

AF:

0.919

GnomAD4 exome

AF:

0.957

AC:

1334998

AN:

1394294

Hom.:

640117

Cov.:

AF XY:

0.957

AC XY:

667658

AN XY:

697786

show subpopulations

Gnomad4 AFR exome

AF:

0.759

Gnomad4 AMR exome

AF:

0.931

Gnomad4 ASJ exome

AF:

0.972

Gnomad4 EAS exome

AF:

0.994

Gnomad4 SAS exome

AF:

0.910

Gnomad4 FIN exome

AF:

0.974

Gnomad4 NFE exome

AF:

0.966

Gnomad4 OTH exome

AF:

0.950

GnomAD4 genome

AF:

0.908

AC:

138259

AN:

152338

Hom.:

63424

Cov.:

AF XY:

0.910

AC XY:

67746

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.766

Gnomad4 AMR

AF:

0.934

Gnomad4 ASJ

AF:

0.975

Gnomad4 EAS

AF:

0.994

Gnomad4 SAS

AF:

0.914

Gnomad4 FIN

AF:

0.974

Gnomad4 NFE

AF:

0.967

Gnomad4 OTH

AF:

0.920

Alfa

AF:

0.940

Hom.:

20021

Bravo

AF:

0.900

Asia WGS

AF:

0.939

AC:

3265

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.6

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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