Genetic Variant POLR2C:p.Val58Val (chr16-57465990-T-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_032940.3(POLR2C):c.174T>A(p.Val58Val) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POLR2C
NM_032940.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0190

Publications

40 publications found

Variant links:

Genes affected

POLR2C (HGNC:9189): (RNA polymerase II subunit C) This gene encodes the third largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a cysteine rich region and exists as a heterodimer with another polymerase subunit, POLR2J. These two subunits form a core subassembly unit of the polymerase. A pseudogene has been identified on chromosome 21. [provided by RefSeq, Jul 2008]

POLR2C links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=-0.019 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032940.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2C	NM_032940.3	MANE Select	c.174T>A	p.Val58Val	synonymous	Exon 3 of 9	NP_116558.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POLR2C	ENST00000219252.10	TSL:1 MANE Select	c.174T>A	p.Val58Val	synonymous	Exon 3 of 9	ENSP00000219252.4
POLR2C	ENST00000562599.5	TSL:5	n.*433T>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000456367.1
POLR2C	ENST00000562953.5	TSL:2	n.232T>A		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1450924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722622

African (AFR)

AF:

0.00

AC:

AN:

33252

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102098

Other (OTH)

AF:

0.00

AC:

AN:

59994

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

67991

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.1

(source)

DANN

Benign

0.88

PhyloP100

-0.019

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over