Genetic Variant NM_006468.8:c.575A>C (chr1-145826991-A-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_006468.8(POLR3C):c.575A>C(p.Lys192Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,609,334 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

POLR3C
NM_006468.8 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.39

Publications

0 publications found

Variant links:

Genes affected

POLR3C (HGNC:30076): (RNA polymerase III subunit C) Enables single-stranded DNA binding activity. Involved in positive regulation of innate immune response and positive regulation of interferon-beta production. Located in nucleoplasm. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

POLR3C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.081481904).

BP6

Variant 1-145826991-A-C is Benign according to our data. Variant chr1-145826991-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3043483.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006468.8. 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
	POLR3C	NM_006468.8	MANE Select	c.575A>C	p.Lys192Thr	missense	Exon 4 of 15	NP_006459.3
	POLR3C	NM_001303456.1		c.614A>C	p.Lys205Thr	missense	Exon 4 of 15	NP_001290385.1	Q9BUI4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLR3C	ENST00000334163.4	TSL:1 MANE Select	c.575A>C	p.Lys192Thr	missense	Exon 4 of 15	ENSP00000334564.3	Q9BUI4
POLR3C	ENST00000369294.5	TSL:1	c.575A>C	p.Lys192Thr	missense	Exon 4 of 12	ENSP00000358300.1	E9PHH9
POLR3C	ENST00000698751.1		c.575A>C	p.Lys192Thr	missense	Exon 4 of 15	ENSP00000513913.1	Q9BUI4

Frequencies

GnomAD3 genomes

AF:

0.000901

AC:

137

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000478

GnomAD2 exomes

AF:

0.000215

AC:

AN:

246802

AF XY:

0.000165

show subpopulations

Gnomad AFR exome

AF:

0.00316

Gnomad AMR exome

AF:

0.0000608

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:

0.00

GnomAD4 exome

AF:

0.0000865

AC:

126

AN:

1457080

Hom.:

Cov.:

AF XY:

0.0000883

AC XY:

AN XY:

724942

show subpopulations

African (AFR)

AF:

0.00317

AC:

105

AN:

33146

American (AMR)

AF:

0.000186

AC:

AN:

42940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25916

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

85254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110764

Other (OTH)

AF:

0.000166

AC:

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000900

AC:

137

AN:

152254

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00322

AC:

134

AN:

41554

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.000388

Hom.:

Bravo

AF:

0.000945

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

POLR3C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

LIST_S2

Benign

0.78

MetaRNN

Benign

0.081

PhyloP100

2.4

PROVEAN

Benign

-0.91

Sift

Benign

0.29

Sift4G

Benign

0.51

Vest4

0.26

gMVP

0.80

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

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