Genetic Variant NM_032305.3:c.500A>G (chr1-145978026-A-G) – 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_032305.3(POLR3GL):c.500A>G(p.Glu167Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000481 in 1,455,772 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: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

POLR3GL
NM_032305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

Publications

0 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: 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=0.19317773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR3GL	NM_032305.3 link	c.500A>G	p.Glu167Gly	missense_variant	Exon 7 of 8	ENST00000369314.2	NP_115681.1	Q9BT43
POLR3GL	NM_001330685.2 link	c.431A>G	p.Glu144Gly	missense_variant	Exon 6 of 7		NP_001317614.1	Q9BT43A6NGX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3GL	ENST00000369314.2 link	c.500A>G	p.Glu167Gly	missense_variant	Exon 7 of 8	1	NM_032305.3	ENSP00000358320.1		Q9BT43
ENSG00000280778	ENST00000625258.1 link	c.*215A>G		downstream_gene_variant		5		ENSP00000487094.1		A0A0D9SG24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248686

AF XY:

0.00000743

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455772

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724632

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33314

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.0000697

AC:

AN:

86100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106666

Other (OTH)

AF:

0.0000166

AC:

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.500A>G (p.E167G) alteration is located in exon 7 (coding exon 6) of the POLR3GL gene. This alteration results from a A to G substitution at nucleotide position 500, causing the glutamic acid (E) at amino acid position 167 to be replaced by a glycine (G). 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

Benign

0.089

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

T;T

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.19

T;T

PhyloP100

5.3

PROVEAN

Uncertain

-2.4

N;N

Sift

Benign

0.13

T;T

Sift4G

Uncertain

0.010

D;T

Vest4

0.39

gMVP

0.084

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over