rs745598020

Variant names:

• chr5-90485670-C-A
• rs745598020
• NM_006467.3:c.103C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90485670-C-A
• chr5-90485670-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006467.3(POLR3G):​c.103C>A​(p.Pro35Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000801 in 1,610,568 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 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: POLR3G NM_006467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17563263).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006467.3. 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
	POLR3G	NM_006467.3	MANE Select	c.103C>A	p.Pro35Thr	missense	Exon 2 of 8	NP_006458.2	O15318
	POLR3G	NM_001370351.1		c.103C>A	p.Pro35Thr	missense	Exon 2 of 8	NP_001357280.1	O15318
	POLR3G	NM_001370354.1		c.103C>A	p.Pro35Thr	missense	Exon 2 of 8	NP_001357283.1	O15318

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3G	ENST00000651687.1	MANE Select	c.103C>A	p.Pro35Thr	missense	Exon 2 of 8	ENSP00000498469.1	O15318
	POLR3G	ENST00000504930.5	TSL:2	c.103C>A	p.Pro35Thr	missense	Exon 2 of 8	ENSP00000421637.1	O15318
	POLR3G	ENST00000859024.1		c.103C>A	p.Pro35Thr	missense	Exon 2 of 8	ENSP00000529083.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000145 AC: 36 AN: 248520 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.000898

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000809 AC: 118 AN: 1458464 Hom.: 0 Cov.: 29 AF XY: 0.0000923 AC XY: 67 AN XY: 725718

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.0000449 AC: 2 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.000690 AC: 18 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.000349 AC: 30 AN: 85950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5754

European-Non Finnish (NFE) AF: 0.0000532 AC: 59 AN: 1109408

Other (OTH) AF: 0.0000995 AC: 6 AN: 60274

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152104 Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6 AN XY: 74282

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autism (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.39
Sift	Benign	0.038	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.56
MVP		0.50
MPC		0.45
ClinPred		0.30	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs745598020; hg19: chr5-89781487;