16-57465990-T-C

Position:

• chr16-57465990-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032940.3(POLR2C):​c.174T>C​(p.Val58Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,600,204 control chromosomes in the GnomAD database, including 442,694 homozygotes. 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: 𝑓 0.78 (47416 hom., cov: 31)
  • Exomes 𝑓: 0.74 (395278 hom.)
• Consequence: POLR2C NM_032940.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.019 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2C	NM_032940.3	c.174T>C	p.Val58Val	synonymous_variant	3/9	ENST00000219252.10	NP_116558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR2C	ENST00000219252.10	c.174T>C	p.Val58Val	synonymous_variant	3/9	1	NM_032940.3	ENSP00000219252.4

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118903 AN: 151952 Hom.: 47365 Cov.: 31

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.782

GnomAD3 exomes AF: 0.714 AC: 179565 AN: 251384 Hom.: 65201 AF XY: 0.718 AC XY: 97507 AN XY: 135882

Gnomad AFR exome AF: 0.938

Gnomad AMR exome AF: 0.588

Gnomad ASJ exome AF: 0.755

Gnomad EAS exome AF: 0.613

Gnomad SAS exome AF: 0.690

Gnomad FIN exome AF: 0.689

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.732

GnomAD4 exome AF: 0.736 AC: 1065680 AN: 1448134 Hom.: 395278 Cov.: 30 AF XY: 0.736 AC XY: 530852 AN XY: 721314

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.762

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.747

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.783 AC: 119017 AN: 152070 Hom.: 47416 Cov.: 31 AF XY: 0.776 AC XY: 57629 AN XY: 74306

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.785

Alfa AF: 0.757 Hom.: 54115

Bravo AF: 0.786

Asia WGS AF: 0.672 AC: 2340 AN: 3478

EpiCase AF: 0.752

EpiControl AF: 0.756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.4
DANN	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs4937; hg19: chr16-57499902; COSMIC: COSV52645059; COSMIC: COSV52645059;