3-52589219-C-G

Position:

• chr3-52589219-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001405601.1(PBRM1):​c.2861G>C​(p.Gly954Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 31)
• Consequence: PBRM1 NM_001405601.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64

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]

PBRM1 (HGNC:):

ACMG classification

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=0.24926087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBRM1	NM_001405601.1	c.2861G>C	p.Gly954Ala	missense_variant	20/32		NP_001392530.1
PBRM1	NM_001405607.1	c.2861G>C	p.Gly954Ala	missense_variant	20/32		NP_001392536.1
PBRM1	NM_001405598.1	c.2843G>C	p.Gly948Ala	missense_variant	19/31		NP_001392527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1	c.2861G>C	p.Gly954Ala	missense_variant	20/32			ENSP00000516722.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;.;T;.;.;.;.;.;.;.
Eigen	Benign	0.031
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	.;N;N;N;N;N;.;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.45	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.47	T;T;T;T;T;T;T;T;.;.
Polyphen		0.40	B;D;P;D;P;P;B;P;B;.
Vest4		0.27
MutPred		0.32		.;Loss of catalytic residue at A938 (P = 0.1188);Loss of catalytic residue at A938 (P = 0.1188);Loss of catalytic residue at A938 (P = 0.1188);Loss of catalytic residue at A938 (P = 0.1188);Loss of catalytic residue at A938 (P = 0.1188);.;.;.;.;
MVP		0.47
MPC		0.58
ClinPred		0.82	D
GERP RS		3.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.13
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs587778591; hg19: chr3-52623235;