Variant 1-171532524-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001387844.1(PRRC2C):c.1436G>C(p.Arg479Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,451,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PRRC2C
NM_001387844.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.77

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42096663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2C	NM_001387844.1 linkuse as main transcript	c.1436G>C	p.Arg479Thr	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.1436G>C	p.Arg479Thr	missense_variant	12/35		NM_001387844.1	ENSP00000495867	A2	Q9Y520-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000862

AC:

AN:

232126

Hom.:

AF XY:

0.00000801

AC XY:

AN XY:

124872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1451978

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.00000824

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

Sep 29, 2023

The c.1430G>C (p.R477T) alteration is located in exon 12 (coding exon 11) of the PRRC2C gene. This alteration results from a G to C substitution at nucleotide position 1430, causing the arginine (R) at amino acid position 477 to be replaced by a threonine (T). 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

Uncertain

0.019

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.096

.;T;.;.

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

D;D;.;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.42

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;.;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-5.5

.;D;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.029

.;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0, 1.0

.;D;D;D

Vest4

0.70, 0.69, 0.73

MutPred

0.27

.;Loss of helix (P = 3e-04);.;.;

MVP

0.18

MPC

0.28

ClinPred

0.31

GERP RS

6.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.2

gMVP

0.52

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