1-156786926-C-T

Position:

• chr1-156786926-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005973.5(PRCC):​c.835C>T​(p.Leu279Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PRCC NM_005973.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39

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 (HGNC:):

ACMG classification

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=0.27880985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRCC	NM_005973.5	c.835C>T	p.Leu279Phe	missense_variant	3/7	ENST00000271526.9	NP_005964.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRCC	ENST00000271526.9	c.835C>T	p.Leu279Phe	missense_variant	3/7	1	NM_005973.5	ENSP00000271526.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.835C>T (p.L279F) alteration is located in exon 3 (coding exon 3) of the PRCC gene. This alteration results from a C to T substitution at nucleotide position 835, causing the leucine (L) at amino acid position 279 to be replaced by a phenylalanine (F). 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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.021	D;T
Polyphen		1.0	D;.
Vest4		0.76
MutPred		0.19		Loss of helix (P = 0.1299);.;
MVP		0.21
MPC		0.86
ClinPred		0.86	D
GERP RS		5.8
Varity_R		0.30
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156756718;