3-52589219-C-G

Variant names:

• chr3-52589219-C-G
• rs587778591
• NM_001405607.1:c.2861G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001405607.1(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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G954V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PBRM1 NM_001405607.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24926087).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405607.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	NM_001405607.1	MANE Select	c.2861G>C	p.Gly954Ala	missense	Exon 20 of 32	NP_001392536.1
	PBRM1	NM_001405601.1		c.2861G>C	p.Gly954Ala	missense	Exon 20 of 32	NP_001392530.1
	PBRM1	NM_001405598.1		c.2843G>C	p.Gly948Ala	missense	Exon 19 of 31	NP_001392527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	ENST00000707071.1	MANE Select	c.2861G>C	p.Gly954Ala	missense	Exon 20 of 32	ENSP00000516722.1
	PBRM1	ENST00000296302.11	TSL:1	c.2816G>C	p.Gly939Ala	missense	Exon 18 of 30	ENSP00000296302.7
	PBRM1	ENST00000409114.7	TSL:1	c.2861G>C	p.Gly954Ala	missense	Exon 19 of 30	ENSP00000386643.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	N
PhyloP100		4.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.054
Sift	Benign	0.45	T
Sift4G	Benign	0.47	T
Polyphen		0.40	B
Vest4		0.27
MutPred		0.32		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
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs587778591; hg19: chr3-52623235;