NM_006466.4:c.106C>G

Variant names:

• chr20-18468987-C-G
• rs1431104589
• NM_006466.4:c.106C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006466.4(POLR3F):​c.106C>G​(p.Gln36Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POLR3F NM_006466.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 101 (varicella zoster virus-specific)

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39713126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006466.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3F	NM_006466.4	MANE Select	c.106C>G	p.Gln36Glu	missense	Exon 2 of 9	NP_006457.2
	POLR3F	NM_001410821.1		c.106C>G	p.Gln36Glu	missense	Exon 2 of 8	NP_001397750.1	A0A8V8TMS0
	POLR3F	NM_001282526.2		c.-18C>G		5_prime_UTR	Exon 2 of 9	NP_001269455.1	Q05DB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3F	ENST00000377603.5	TSL:1 MANE Select	c.106C>G	p.Gln36Glu	missense	Exon 2 of 9	ENSP00000366828.4	Q9H1D9
	POLR3F	ENST00000462997.6	TSL:1	c.-18C>G		5_prime_UTR	Exon 2 of 9	ENSP00000513375.1	Q05DB8
	POLR3F	ENST00000697647.1		c.106C>G	p.Gln36Glu	missense	Exon 2 of 10	ENSP00000513371.1	A0A8V8TLI4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.076
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.72	N
PhyloP100		7.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.21
Sift	Benign	0.64	T
Sift4G	Benign	0.78	T
Polyphen		0.0010	B
Vest4		0.69
MVP		0.46
MPC		0.69
ClinPred		0.94	D
GERP RS		6.1
Varity_R		0.20
gMVP		0.44
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs1431104589; hg19: chr20-18449631;