3-52563415-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The ENST00000707071.1(PBRM1):c.3999G>T(p.Glu1333Asp) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PBRM1 ENST00000707071.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.573

Genes affected

PBRM1 (HGNC:30064): (polybromo 1) This locus encodes a subunit of ATP-dependent chromatin-remodeling complexes. The encoded protein has been identified as in integral component of complexes necessary for ligand-dependent transcriptional activation by nuclear hormone receptors. Mutations at this locus have been associated with primary clear cell renal cell carcinoma. [provided by RefSeq, Feb 2012]

UQCC5 (HGNC:37257): (ubiquinol-cytochrome c reductase complex assembly factor 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PBRM1
• BP4: Computational evidence support a benign effect (MetaRNN=0.09379983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.3999G>T	p.Glu1333Asp	missense_variant	26/32	ENST00000707071.1
PBRM1	NR_175959.1	n.4176G>T		non_coding_transcript_exon_variant	26/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.3999G>T	p.Glu1333Asp	missense_variant	26/32		NM_001405607.1	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

research

Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo

Feb 08, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	20
Dann	Benign	0.80
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.094	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.65	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.15	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.42	T;T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;.
Polyphen		0.0010	B;B;B;B;B;B;B;B;.
Vest4		0.16
MutPred		0.18		.;.;Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;.;.;.;
MVP		0.38
MPC		0.81
ClinPred		0.76	D
GERP RS		4.8
Varity_R		0.085
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52597431;