1-145825868-C-A

Variant names:

• chr1-145825868-C-A
• rs587726704
• NM_006468.8:c.92C>A

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.92C>A​(p.Thr31Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T31I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POLR3C NM_006468.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• 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=0.10605055).

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.92C>A	p.Thr31Asn	missense	Exon 2 of 15	NP_006459.3
	POLR3C	NM_001303456.1		c.131C>A	p.Thr44Asn	missense	Exon 2 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.92C>A	p.Thr31Asn	missense	Exon 2 of 15	ENSP00000334564.3	Q9BUI4
	POLR3C	ENST00000369294.5	TSL:1	c.92C>A	p.Thr31Asn	missense	Exon 2 of 12	ENSP00000358300.1	E9PHH9
	POLR3C	ENST00000698751.1		c.92C>A	p.Thr31Asn	missense	Exon 2 of 15	ENSP00000513913.1	Q9BUI4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461132 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726904

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111352

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0012	T
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.11	T
PhyloP100		3.0
PROVEAN	Benign	0.34	N
Sift	Benign	0.44	T
Sift4G	Benign	0.60	T
Vest4		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.74

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: rs587726704; hg19: chr1-145609245;