Genetic Variant NM_006466.4:c.249-8C>T (chr20-18473383-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006466.4(POLR3F):c.249-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,195,844 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 1 hom. )

Consequence

POLR3F
NM_006466.4 splice_region, intron

Scores

Splicing: ADA: 0.00007181

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.593

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 101 (varicella zoster virus-specific)
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

POLR3F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 20-18473383-C-T is Benign according to our data. Variant chr20-18473383-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2069957.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POLR3F	NM_006466.4	MANE Select	c.249-8C>T	splice_region intron	N/A	NP_006457.2
POLR3F	NM_001282526.2		c.126-8C>T	splice_region intron	N/A	NP_001269455.1	Q05DB8
POLR3F	NM_001410821.1		c.249-8C>T	splice_region intron	N/A	NP_001397750.1	A0A8V8TMS0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POLR3F	ENST00000377603.5	TSL:1 MANE Select	c.249-8C>T	splice_region intron	N/A	ENSP00000366828.4	Q9H1D9
POLR3F	ENST00000462997.6	TSL:1	c.126-8C>T	splice_region intron	N/A	ENSP00000513375.1	Q05DB8
POLR3F	ENST00000697647.1		c.249-8C>T	splice_region intron	N/A	ENSP00000513371.1	A0A8V8TLI4

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.0000443

AC:

AN:

248192

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.000206

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.0000393

AC:

AN:

1043778

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

538056

show subpopulations

African (AFR)

AF:

0.0000395

AC:

AN:

25296

American (AMR)

AF:

0.000620

AC:

AN:

43580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23324

East Asian (EAS)

AF:

0.00

AC:

AN:

37656

South Asian (SAS)

AF:

0.00

AC:

AN:

77080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4940

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

733118

Other (OTH)

AF:

0.000281

AC:

AN:

46322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000276

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41454

American (AMR)

AF:

0.00242

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.000824

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.0

(source)

DANN

Benign

0.45

PhyloP100

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000072

dbscSNV1_RF

Benign

0.0060

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over