16-57465990-T-C

Variant names:

• chr16-57465990-T-C
• rs4937
• NM_032940.3:c.174T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 40 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

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>C	p.Val58Val	synonymous	Exon 3 of 9	NP_116558.1

Ensembl Transcripts

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

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

GnomAD2 exomes AF: 0.714 AC: 179565 AN: 251384 AF XY: 0.718

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 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

African (AFR) AF: 0.940 AC: 31257 AN: 33240

American (AMR) AF: 0.597 AC: 26658 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 19829 AN: 26034

East Asian (EAS) AF: 0.537 AC: 21299 AN: 39636

South Asian (SAS) AF: 0.696 AC: 59854 AN: 85952

European-Finnish (FIN) AF: 0.687 AC: 36677 AN: 53412

Middle Eastern (MID) AF: 0.736 AC: 4207 AN: 5714

European-Non Finnish (NFE) AF: 0.747 AC: 821172 AN: 1099536

Other (OTH) AF: 0.746 AC: 44727 AN: 59920

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

African (AFR) AF: 0.932 AC: 38672 AN: 41508

American (AMR) AF: 0.684 AC: 10449 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2647 AN: 3472

East Asian (EAS) AF: 0.605 AC: 3130 AN: 5172

South Asian (SAS) AF: 0.696 AC: 3344 AN: 4808

European-Finnish (FIN) AF: 0.683 AC: 7206 AN: 10552

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51039 AN: 67962

Other (OTH) AF: 0.785 AC: 1656 AN: 2110

Alfa AF: 0.761 Hom.: 67991

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.4
DANN	Benign	0.86
PhyloP100		-0.019
Mutation Taster		=96/4	polymorphism (auto)

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