Variant 5-90488019-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006467.3(POLR3G):c.137T>A(p.Val46Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,602,354 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

POLR3G
NM_006467.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

POLR3G (HGNC:30075): (RNA polymerase III subunit G) Enables chromatin binding activity. Involved in positive regulation of innate immune response; positive regulation of interferon-beta production; and transcription by RNA polymerase III. Acts upstream of or within cell population proliferation. Located in cytosol and nuclear body. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

POLR3G links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR3G	NM_006467.3 linkuse as main transcript	c.137T>A	p.Val46Glu	missense_variant	3/8	ENST00000651687.1	NP_006458.2	O15318A0A024RAM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR3G	ENST00000651687.1 linkuse as main transcript	c.137T>A	p.Val46Glu	missense_variant	3/8		NM_006467.3	ENSP00000498469.1		O15318

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1450158

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

721338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000217

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.137T>A (p.V46E) alteration is located in exon 3 (coding exon 2) of the POLR3G gene. This alteration results from a T to A substitution at nucleotide position 137, causing the valine (V) at amino acid position 46 to be replaced by a glutamic acid (E). 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

Pathogenic

0.61

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;T;T;T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

D;D;D;D;.;D

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.49

T;T;T;T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Pathogenic

3.3

.;.;.;M;M;.

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.8

D;D;D;D;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.013

D;D;D;D;D;D

Sift4G

Uncertain

0.0030

D;T;D;T;T;D

Polyphen

1.0

.;.;.;D;D;.

Vest4

0.78, 0.77

MutPred

0.34

Gain of ubiquitination at K44 (P = 0.0919);Gain of ubiquitination at K44 (P = 0.0919);Gain of ubiquitination at K44 (P = 0.0919);Gain of ubiquitination at K44 (P = 0.0919);Gain of ubiquitination at K44 (P = 0.0919);Gain of ubiquitination at K44 (P = 0.0919);

MVP

0.64

MPC

0.54

ClinPred

1.0

GERP RS

4.4

Varity_R

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over