Variant chr1-171532799-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387844.1(PRRC2C):c.1711C>T(p.Arg571Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 1,566,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

PRRC2C
NM_001387844.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.488

Variant links:

Genes affected

PRRC2C (HGNC:24903): (proline rich coiled-coil 2C) Enables protein C-terminus binding activity. Involved in stress granule assembly. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PRRC2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015875578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2C	NM_001387844.1 linkuse as main transcript	c.1711C>T	p.Arg571Trp	missense_variant	12/35	ENST00000647382.2	NP_001374773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2C	ENST00000647382.2 linkuse as main transcript	c.1711C>T	p.Arg571Trp	missense_variant	12/35		NM_001387844.1	ENSP00000495867	A2	Q9Y520-7

Frequencies

GnomAD3 genomes

AF:

0.000113

AC:

AN:

150850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000537

AC:

AN:

186234

Hom.:

AF XY:

0.0000502

AC XY:

AN XY:

99608

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000126

Gnomad OTH exome

AF:

0.000407

GnomAD4 exome

AF:

0.0000318

AC:

AN:

1415578

Hom.:

Cov.:

AF XY:

0.0000314

AC XY:

AN XY:

700574

show subpopulations

Gnomad4 AFR exome

AF:

0.000319

Gnomad4 AMR exome

AF:

0.000143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000521

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000220

Gnomad4 OTH exome

AF:

0.0000511

GnomAD4 genome

AF:

0.000113

AC:

AN:

150850

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

73542

show subpopulations

Gnomad4 AFR

AF:

0.000293

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000762

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.000684

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000252

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.1705C>T (p.R569W) alteration is located in exon 12 (coding exon 11) of the PRRC2C gene. This alteration results from a C to T substitution at nucleotide position 1705, causing the arginine (R) at amino acid position 569 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.036

T;.;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.83

T;.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

.;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.046

Sift

Benign

0.054

T;T;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.0010

B;B;B

Vest4

0.13

MVP

0.043

MPC

0.19

ClinPred

0.14

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.012

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