Variant 1-171588461-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001387844.1(PRRC2C):c.8155A>G(p.Thr2719Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,613,710 control chromosomes in the GnomAD database, including 1,309 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.028 ( 96 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1213 hom. )

Consequence

PRRC2C
NM_001387844.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.15

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018080473).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0282 (4291/152310) while in subpopulation SAS AF= 0.0433 (209/4824). AF 95% confidence interval is 0.0398. There are 96 homozygotes in gnomad4. There are 2076 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 96 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2C	NM_001387844.1 linkuse as main transcript	c.8155A>G	p.Thr2719Ala	missense_variant	33/35	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.8155A>G	p.Thr2719Ala	missense_variant	33/35		NM_001387844.1	ENSP00000495867	A2	Q9Y520-7

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4288

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0328

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0425

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0411

Gnomad OTH

AF:

0.0273

GnomAD3 exomes

AF:

0.0327

AC:

8207

AN:

250838

Hom.:

175

AF XY:

0.0345

AC XY:

4680

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.00536

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0287

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0438

Gnomad FIN exome

AF:

0.0506

Gnomad NFE exome

AF:

0.0416

Gnomad OTH exome

AF:

0.0322

GnomAD4 exome

AF:

0.0389

AC:

56856

AN:

1461400

Hom.:

1213

Cov.:

AF XY:

0.0392

AC XY:

28499

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.00559

Gnomad4 AMR exome

AF:

0.0147

Gnomad4 ASJ exome

AF:

0.0313

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0450

Gnomad4 FIN exome

AF:

0.0497

Gnomad4 NFE exome

AF:

0.0418

Gnomad4 OTH exome

AF:

0.0333

GnomAD4 genome

AF:

0.0282

AC:

4291

AN:

152310

Hom.:

Cov.:

AF XY:

0.0279

AC XY:

2076

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00604

Gnomad4 AMR

AF:

0.0223

Gnomad4 ASJ

AF:

0.0328

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0433

Gnomad4 FIN

AF:

0.0488

Gnomad4 NFE

AF:

0.0411

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0377

Hom.:

313

Bravo

AF:

0.0248

TwinsUK

AF:

0.0351

AC:

130

ALSPAC

AF:

0.0306

AC:

118

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0388

AC:

334

ExAC

AF:

0.0326

AC:

3952

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0399

EpiControl

AF:

0.0399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.0039

T;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

T;.;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.64

N;N;.

REVEL

Benign

0.10

Sift

Benign

0.34

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0040

.;B;B

Vest4

0.050

MPC

0.20

ClinPred

0.0095

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.14

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over