Genetic Variant POLR3GL:p.Arg10His (chr1-145974894-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_032305.3(POLR3GL):c.29G>A(p.Arg10His) variant causes a missense change. The variant allele was found at a frequency of 0.00019 in 1,518,848 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 (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

POLR3GL
NM_032305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Publications

3 publications found

Variant links:

Genes affected

POLR3GL (HGNC:28466): (RNA polymerase III subunit GL) Predicted to enable chromatin binding activity. Involved in transcription by RNA polymerase III. Located in nucleus. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

POLR3GL links:

ENSG00000280778 (HGNC:):

ENSG00000280778 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3638371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR3GL	NM_032305.3 link	c.29G>A	p.Arg10His	missense_variant	Exon 2 of 8	ENST00000369314.2	NP_115681.1	Q9BT43
POLR3GL	NM_001330685.2 link	c.29G>A	p.Arg10His	missense_variant	Exon 2 of 7		NP_001317614.1	Q9BT43A6NGX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3GL	ENST00000369314.2 link	c.29G>A	p.Arg10His	missense_variant	Exon 2 of 8	1	NM_032305.3	ENSP00000358320.1		Q9BT43
ENSG00000280778	ENST00000625258.1 link	c.-29-2190G>A		intron_variant	Intron 1 of 3	5		ENSP00000487094.1		A0A0D9SG24

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000154

AC:

AN:

156130

AF XY:

0.000115

show subpopulations

Gnomad AFR exome

AF:

0.000108

Gnomad AMR exome

AF:

0.000877

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.000615

GnomAD4 exome

AF:

0.000200

AC:

274

AN:

1366610

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

111

AN XY:

675686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27828

American (AMR)

AF:

0.000712

AC:

AN:

22464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22940

East Asian (EAS)

AF:

0.00

AC:

AN:

33614

South Asian (SAS)

AF:

0.0000141

AC:

AN:

70894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5496

European-Non Finnish (NFE)

AF:

0.000231

AC:

248

AN:

1075238

Other (OTH)

AF:

0.000160

AC:

AN:

56186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.0000869

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.29G>A (p.R10H) alteration is located in exon 2 (coding exon 1) of the POLR3GL gene. This alteration results from a G to A substitution at nucleotide position 29, causing the arginine (R) at amino acid position 10 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_noAF

Pathogenic

0.59

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;T

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.36

T;T

PhyloP100

6.8

PROVEAN

Uncertain

-4.0

D;D

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.015

D;D

Vest4

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.59

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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chr1-145974894-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over