chr16-22309025-C-T

Variant names:

• chr16-22309025-C-T
• NM_018119.4:c.266C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018119.4(POLR3E):​c.266C>T​(p.Thr89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: POLR3E NM_018119.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14
• Publications: 0 publications found

Genes affected

POLR3E (HGNC:30347): (RNA polymerase III subunit E) Predicted to enable DNA-directed 5'-3' RNA polymerase activity. Predicted to be involved in defense response to virus; innate immune response; and transcription, DNA-templated. 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2775175).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018119.4. 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
	POLR3E	NM_018119.4	MANE Select	c.266C>T	p.Thr89Ile	missense	Exon 5 of 21	NP_060589.1	Q9NVU0-1
	POLR3E	NM_001258033.2		c.266C>T	p.Thr89Ile	missense	Exon 5 of 21	NP_001244962.1	Q9NVU0-4
	POLR3E	NM_001258034.2		c.158C>T	p.Thr53Ile	missense	Exon 4 of 20	NP_001244963.1	Q9NVU0-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3E	ENST00000299853.10	TSL:1 MANE Select	c.266C>T	p.Thr89Ile	missense	Exon 5 of 21	ENSP00000299853.5	Q9NVU0-1
	POLR3E	ENST00000359210.8	TSL:1	c.266C>T	p.Thr89Ile	missense	Exon 5 of 20	ENSP00000352140.4	Q9NVU0-2
	POLR3E	ENST00000564061.5	TSL:1	n.387C>T		non_coding_transcript_exon	Exon 5 of 18

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.22
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.13
Sift	Benign	0.057	T
Sift4G	Uncertain	0.028	D
Polyphen		0.54	P
Vest4		0.60
MutPred		0.45		Loss of helix (P = 0.0123)
MVP		0.72
MPC		0.58
ClinPred		0.89	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.40

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

hg19: chr16-22320346;