Variant 20-18472906-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006466.4(POLR3F):c.245C>G(p.Ala82Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000566 in 1,236,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

POLR3F
NM_006466.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.27

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR3F	NM_006466.4 linkuse as main transcript	c.245C>G	p.Ala82Gly	missense_variant	3/9	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.245C>G	p.Ala82Gly	missense_variant	3/9	1	NM_006466.4	ENSP00000366828.4		Q9H1D9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000435

AC:

AN:

229636

Hom.:

AF XY:

0.00000800

AC XY:

AN XY:

125038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000932

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000566

AC:

AN:

1236916

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

624950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000758

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

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

Feb 27, 2023

The c.245C>G (p.A82G) alteration is located in exon 3 (coding exon 3) of the POLR3F gene. This alteration results from a C to G substitution at nucleotide position 245, causing the alanine (A) at amino acid position 82 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

0.0084

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.85

M_CAP

Benign

0.0043

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.9

REVEL

Benign

0.13

Sift

Benign

0.091

Sift4G

Benign

0.14

Polyphen

0.0050

Vest4

0.46

MutPred

0.57

Loss of helix (P = 0.0558);

MVP

0.70

MPC

0.65

ClinPred

0.69

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.39

Position offset: -1

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