5-90485154-C-T

Variant names:

• chr5-90485154-C-T
• rs2562519
• NM_006467.3:c.-43-371C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006467.3(POLR3G):​c.-43-371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,110 control chromosomes in the GnomAD database, including 38,290 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (38290 hom., cov: 32)
• Consequence: POLR3G NM_006467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3G	NM_006467.3	MANE Select	c.-43-371C>T		intron	N/A	NP_006458.2
	POLR3G	NM_001370351.1		c.-33-381C>T		intron	N/A	NP_001357280.1
	POLR3G	NM_001370354.1		c.-43-371C>T		intron	N/A	NP_001357283.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3G	ENST00000651687.1	MANE Select	c.-43-371C>T		intron	N/A	ENSP00000498469.1
	POLR3G	ENST00000504930.5	TSL:2	c.-33-381C>T		intron	N/A	ENSP00000421637.1
	POLR3G	ENST00000503373.5	TSL:4	c.-43-371C>T		intron	N/A	ENSP00000422892.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107121 AN: 151992 Hom.: 38276 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.728

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.705 AC: 107174 AN: 152110 Hom.: 38290 Cov.: 32 AF XY: 0.704 AC XY: 52316 AN XY: 74340

African (AFR) AF: 0.583 AC: 24199 AN: 41474

American (AMR) AF: 0.775 AC: 11835 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2631 AN: 3470

East Asian (EAS) AF: 0.668 AC: 3456 AN: 5176

South Asian (SAS) AF: 0.677 AC: 3264 AN: 4824

European-Finnish (FIN) AF: 0.746 AC: 7885 AN: 10570

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51508 AN: 68002

Other (OTH) AF: 0.728 AC: 1540 AN: 2114

Alfa AF: 0.745 Hom.: 138427

Bravo AF: 0.702

Asia WGS AF: 0.661 AC: 2304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs2562519; hg19: chr5-89780971;