rs587778592

Positions:

• chr3-52662252-C-A
• chr3-52662252-C-G
• chr3-52662252-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000707071.1(PBRM1):​c.409G>T​(p.Ala137Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PBRM1 ENST00000707071.1 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 7.36

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBRM1	NM_001405607.1	c.409G>T	p.Ala137Ser	missense_variant	5/32	ENST00000707071.1	NP_001392536.1
PBRM1	NR_175959.1	n.586G>T		non_coding_transcript_exon_variant	5/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1	c.409G>T	p.Ala137Ser	missense_variant	5/32		NM_001405607.1	ENSP00000516722	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;.;T;.;.;.;.;.;.;.;T;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M;M;M;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;.;.;.;.
Polyphen		1.0	D;D;D;D;D;D;D;D;.;.;.;.
Vest4		0.74
MutPred		0.76		Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);.;Gain of disorder (P = 0.0727);Gain of disorder (P = 0.0727);
MVP		0.57
MPC		1.1
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs587778592; hg19: chr3-52696268;