Variant 1-156786792-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005973.5(PRCC):c.701G>T(p.Gly234Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 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: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRCC
NM_005973.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21829122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRCC	NM_005973.5 linkuse as main transcript	c.701G>T	p.Gly234Val	missense_variant	3/7	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.701G>T	p.Gly234Val	missense_variant	3/7	1	NM_005973.5	ENSP00000271526.4	Q92733
PRCC	ENST00000473387.1 linkuse as main transcript	n.264G>T		non_coding_transcript_exon_variant	3/3	2
PRCC	ENST00000491853.5 linkuse as main transcript	n.355G>T		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

Jun 04, 2024

The c.701G>T (p.G234V) alteration is located in exon 3 (coding exon 3) of the PRCC gene. This alteration results from a G to T substitution at nucleotide position 701, causing the glycine (G) at amino acid position 234 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.83

M_CAP

Benign

0.0070

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.060

REVEL

Benign

0.042

Sift

Benign

0.086

Sift4G

Benign

0.080

Polyphen

0.99

Vest4

0.21

MutPred

0.30

Gain of sheet (P = 0.0049);

MVP

0.13

MPC

0.69

ClinPred

0.56

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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