5-90507770-T-C

Variant names:

• chr5-90507770-T-C
• rs3805483
• NM_006467.3:c.585+1096T>C

Variant summary

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

The NM_006467.3(POLR3G):​c.585+1096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,052 control chromosomes in the GnomAD database, including 12,997 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 0.41 (12997 hom., cov: 32)
• Consequence: POLR3G NM_006467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3G	NM_006467.3	MANE Select	c.585+1096T>C		intron	N/A	NP_006458.2	O15318
	POLR3G	NM_001370351.1		c.585+1096T>C		intron	N/A	NP_001357280.1	O15318
	POLR3G	NM_001370354.1		c.585+1096T>C		intron	N/A	NP_001357283.1	O15318

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3G	ENST00000651687.1	MANE Select	c.585+1096T>C		intron	N/A	ENSP00000498469.1	O15318
	POLR3G	ENST00000504930.5	TSL:2	c.585+1096T>C		intron	N/A	ENSP00000421637.1	O15318
	POLR3G	ENST00000859024.1		c.585+1096T>C		intron	N/A	ENSP00000529083.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61730 AN: 151934 Hom.: 12992 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.406 AC: 61746 AN: 152052 Hom.: 12997 Cov.: 32 AF XY: 0.401 AC XY: 29795 AN XY: 74332

African (AFR) AF: 0.332 AC: 13756 AN: 41466

American (AMR) AF: 0.323 AC: 4936 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1450 AN: 3464

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5174

South Asian (SAS) AF: 0.414 AC: 1995 AN: 4824

European-Finnish (FIN) AF: 0.446 AC: 4707 AN: 10546

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32405 AN: 67970

Other (OTH) AF: 0.401 AC: 847 AN: 2112

Alfa AF: 0.454 Hom.: 10079

Bravo AF: 0.390

Asia WGS AF: 0.287 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.7
DANN	Benign	0.77
PhyloP100		0.45
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: rs3805483; hg19: chr5-89803587;