1-145977491-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032305.3(POLR3GL):​c.334C>T​(p.Arg112Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

POLR3GL
NM_032305.3 missense

Scores

4
3
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POLR3GLNM_032305.3 linkc.334C>T p.Arg112Cys missense_variant Exon 5 of 8 ENST00000369314.2 NP_115681.1 Q9BT43
POLR3GLNM_001330685.2 linkc.265C>T p.Arg89Cys missense_variant Exon 4 of 7 NP_001317614.1 Q9BT43A6NGX6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POLR3GLENST00000369314.2 linkc.334C>T p.Arg112Cys missense_variant Exon 5 of 8 1 NM_032305.3 ENSP00000358320.1 Q9BT43
ENSG00000280778ENST00000625258.1 linkc.49C>T p.Arg17Cys missense_variant Exon 3 of 4 5 ENSP00000487094.1 A0A0D9SG24

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152108
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
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:
0.0000109
AC:
16
AN:
1461684
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727166
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:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152108
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 01, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.334C>T (p.R112C) alteration is located in exon 5 (coding exon 4) of the POLR3GL gene. This alteration results from a C to T substitution at nucleotide position 334, causing the arginine (R) at amino acid position 112 to be replaced by a cysteine (C). 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
0.11
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
.;T;T
LIST_S2
Uncertain
0.89
D;D;D
MetaRNN
Pathogenic
0.80
D;D;D
PROVEAN
Pathogenic
-5.2
.;D;D
Sift
Uncertain
0.0010
.;D;D
Sift4G
Uncertain
0.020
D;T;T
Vest4
0.33, 0.34
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.81

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.

Other links and lift over

dbSNP: rs1276652879; hg19: chr1-145457596; API