Genetic Variant NM_001722.3:c.50G>A (chr8-22245499-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001722.3(POLR3D):c.50G>A(p.Arg17Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000809 in 1,297,864 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17L) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

POLR3D
NM_001722.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16878384).

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.50G>A	p.Arg17Gln	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.50G>A	p.Arg17Gln	missense	Exon 2 of 9	ENSP00000303088.4	P05423
POLR3D	ENST00000397802.8	TSL:1	c.50G>A	p.Arg17Gln	missense	Exon 1 of 8	ENSP00000380904.3	P05423
POLR3D	ENST00000861620.1		c.50G>A	p.Arg17Gln	missense	Exon 2 of 9	ENSP00000531679.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000489

AC:

AN:

81820

AF XY:

0.0000219

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000175

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000695

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000838

AC:

AN:

1145722

Hom.:

Cov.:

AF XY:

0.0000859

AC XY:

AN XY:

547006

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

24638

American (AMR)

AF:

0.0000628

AC:

AN:

15934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14980

East Asian (EAS)

AF:

0.0000667

AC:

AN:

29974

South Asian (SAS)

AF:

0.00

AC:

AN:

25252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3672

European-Non Finnish (NFE)

AF:

0.0000897

AC:

AN:

947588

Other (OTH)

AF:

0.000110

AC:

AN:

45592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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:

152142

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41440

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68006

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000277

AC:

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

0.23

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.1

PhyloP100

4.6

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.12

REVEL

Benign

0.12

Sift

Benign

0.54

Sift4G

Benign

0.64

Polyphen

1.0

Vest4

0.47

MVP

0.37

MPC

0.36

ClinPred

0.24

GERP RS

5.6

PromoterAI

-0.029

Neutral

(source)

Varity_R

0.10

gMVP

0.35

Mutation Taster

=82/18

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

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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