Variant 16-57462801-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BS2_Supporting

The NM_032940.3(POLR2C):c.77C>G(p.Thr26Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,607,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

POLR2C
NM_032940.3 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.32

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5

Variant 16-57462801-C-G is Pathogenic according to our data. Variant chr16-57462801-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1256028.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2C	NM_032940.3 link	c.77C>G	p.Thr26Ser	missense_variant	1/9	ENST00000219252.10	NP_116558.1	P19387Q6FGR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR2C	ENST00000219252.10 link	c.77C>G	p.Thr26Ser	missense_variant	1/9	1	NM_032940.3	ENSP00000219252.4		P19387

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000875

AC:

AN:

239890

Hom.:

AF XY:

0.0000922

AC XY:

AN XY:

130144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00117

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1455210

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

723546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000607

Gnomad4 SAS exome

AF:

0.0000587

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000967

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.0000578

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Genetic non-acquired premature ovarian failure

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University

Oct 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.29

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

0.49

MutationAssessor

Uncertain

2.5

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.64

Sift

Uncertain

0.0060

Sift4G

Benign

0.075

Polyphen

0.93

Vest4

0.83

MutPred

0.50

Gain of relative solvent accessibility (P = 0.1571);

MVP

0.98

MPC

1.6

ClinPred

0.43

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over