1-145828803-C-G

Variant names:

• chr1-145828803-C-G
• rs782234829
• NM_006468.8:c.644C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006468.8(POLR3C):​c.644C>G​(p.Ala215Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLR3C NM_006468.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63
• Publications: 0 publications found

Genes affected

POLR3C (HGNC:30076): (RNA polymerase III subunit C) Enables single-stranded DNA binding activity. Involved in positive regulation of innate immune response and positive regulation of interferon-beta production. Located in nucleoplasm. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.16999489).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006468.8. 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
	POLR3C	NM_006468.8	MANE Select	c.644C>G	p.Ala215Gly	missense	Exon 5 of 15	NP_006459.3
	POLR3C	NM_001303456.1		c.683C>G	p.Ala228Gly	missense	Exon 5 of 15	NP_001290385.1	Q9BUI4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3C	ENST00000334163.4	TSL:1 MANE Select	c.644C>G	p.Ala215Gly	missense	Exon 5 of 15	ENSP00000334564.3	Q9BUI4
	POLR3C	ENST00000369294.5	TSL:1	c.644C>G	p.Ala215Gly	missense	Exon 5 of 12	ENSP00000358300.1	E9PHH9
	POLR3C	ENST00000698751.1		c.644C>G	p.Ala215Gly	missense	Exon 5 of 15	ENSP00000513913.1	Q9BUI4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.17	T
PhyloP100		4.6
PROVEAN	Benign	-1.2	N
Sift	Benign	0.030	D
Sift4G	Benign	0.076	T
Vest4		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.75

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: rs782234829; hg19: chr1-145606309;