NM_006468.8:c.190_192delAGTinsTGC

Variant names:

• chr1-145826496-AGT-TGC
• NM_006468.8:c.190_192delAGTinsTGC
• POLR3C p.Ser64Cys

Variant summary

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

The NM_006468.8(POLR3C):​c.190_192delAGTinsTGC​(p.Ser64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S64T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLR3C NM_006468.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• 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.

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.190_192delAGTinsTGC	p.Ser64Cys	missense	N/A	NP_006459.3
	POLR3C	NM_001303456.1		c.229_231delAGTinsTGC	p.Ser77Cys	missense	N/A	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.190_192delAGTinsTGC	p.Ser64Cys	missense	N/A	ENSP00000334564.3	Q9BUI4
	POLR3C	ENST00000369294.5	TSL:1	c.190_192delAGTinsTGC	p.Ser64Cys	missense	N/A	ENSP00000358300.1	E9PHH9
	POLR3C	ENST00000698751.1		c.190_192delAGTinsTGC	p.Ser64Cys	missense	N/A	ENSP00000513913.1	Q9BUI4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-145608617;