Genetic Variant POLR3D:p.Arg24Gly (chr8-22245519-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001722.3(POLR3D):c.70C>G(p.Arg24Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,280,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

POLR3D
NM_001722.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Publications

0 publications found

Variant links:

Genes affected

POLR3D (HGNC:1080): (RNA polymerase III subunit D) This gene complements a temperature-sensitive mutant isolated from the BHK-21 Syrian hamster cell line. It leads to a block in progression through the G1 phase of the cell cycle at nonpermissive temperatures. [provided by RefSeq, Jul 2008]

POLR3D links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22086242).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001722.3. 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
	POLR3D	NM_001722.3	MANE Select	c.70C>G	p.Arg24Gly	missense	Exon 2 of 9	NP_001713.2	P05423

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLR3D	ENST00000306433.9	TSL:1 MANE Select	c.70C>G	p.Arg24Gly	missense	Exon 2 of 9	ENSP00000303088.4	P05423
POLR3D	ENST00000397802.8	TSL:1	c.70C>G	p.Arg24Gly	missense	Exon 1 of 8	ENSP00000380904.3	P05423
POLR3D	ENST00000861620.1		c.70C>G	p.Arg24Gly	missense	Exon 2 of 9	ENSP00000531679.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000443

AC:

AN:

1128518

Hom.:

Cov.:

AF XY:

0.00000373

AC XY:

AN XY:

536836

show subpopulations

African (AFR)

AF:

0.0000823

AC:

AN:

24300

American (AMR)

AF:

0.000150

AC:

AN:

13358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14718

East Asian (EAS)

AF:

0.00

AC:

AN:

28984

South Asian (SAS)

AF:

0.00

AC:

AN:

22994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3938

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

938366

Other (OTH)

AF:

0.0000222

AC:

AN:

45002

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

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:

0.0000592

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000843

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.016

Eigen

Benign

-0.047

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.73

M_CAP

Benign

0.0087

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.76

PhyloP100

2.1

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.69

REVEL

Benign

0.056

Sift

Uncertain

0.0040

Sift4G

Benign

0.22

Polyphen

0.32

Vest4

0.62

MutPred

0.32

Loss of methylation at R24 (P = 0.0069)

MVP

0.63

MPC

0.29

ClinPred

0.67

GERP RS

5.6

PromoterAI

-0.021

Neutral

(source)

Varity_R

0.24

gMVP

0.51

Mutation Taster

=70/30

polymorphism

(source)

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