Variant 1-156767832-C-G 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_005973.5(PRCC):c.61C>G(p.Pro21Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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

PRCC
NM_005973.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

PRCC (HGNC:9343): (proline rich mitotic checkpoint control factor) This gene encodes a protein that may play a role in pre-mRNA splicing. Chromosomal translocations (X;1)(p11;q21) that result in fusion of this gene to TFE3 (GeneID 7030) have been associated with papillary renal cell carcinoma. A PRCC-TFE3 fusion protein is expressed in affected carcinomas and is likely associated with altered gene transactivation. This fusion protein has also been associated with disruption of the cell cycle.[provided by RefSeq, Aug 2010]

PRCC links:

PRCC (HGNC:):

PRCC links:

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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=0.06416136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRCC	NM_005973.5 linkuse as main transcript	c.61C>G	p.Pro21Ala	missense_variant	1/7	ENST00000271526.9	NP_005964.3	Q92733A0A0S2Z456Q96FT4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRCC	ENST00000271526.9 linkuse as main transcript	c.61C>G	p.Pro21Ala	missense_variant	1/7	1	NM_005973.5	ENSP00000271526.4	Q92733
PRCC	ENST00000473387.1 linkuse as main transcript	n.31+249C>G		intron_variant		2
PRCC	ENST00000491853.5 linkuse as main transcript	n.123-14450C>G		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000828

AC:

AN:

241638

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131600

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

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:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458210

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Dec 14, 2023

The c.61C>G (p.P21A) alteration is located in exon 1 (coding exon 1) of the PRCC gene. This alteration results from a C to G substitution at nucleotide position 61, causing the proline (P) at amino acid position 21 to be replaced by an alanine (A). 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

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.034

Eigen

Benign

-0.12

Eigen_PC

Benign

0.045

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.65

M_CAP

Benign

0.0020

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.53

REVEL

Benign

0.028

Sift

Benign

0.43

Sift4G

Benign

0.38

Polyphen

0.071

Vest4

0.17

MutPred

0.098

Gain of helix (P = 0.0128);

MVP

0.10

MPC

0.21

ClinPred

0.16

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.14

gMVP

0.26

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