3-52648421-G-C

Variant summary

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

The ENST00000707071.1(PBRM1):c.736C>G(p.His246Asp) 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. 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. H246N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PBRM1 ENST00000707071.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58

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 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=0.20214728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.736C>G	p.His246Asp	missense_variant	8/32	ENST00000707071.1
PBRM1	NR_175959.1	n.913C>G		non_coding_transcript_exon_variant	8/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.736C>G	p.His246Asp	missense_variant	8/32		NM_001405607.1	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
Cadd	Pathogenic	26
Dann	Uncertain	0.98
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N;N;N;N;N;N;N;N;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.77	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.59	T;T;T;T;T;T;T;T;.;.
Polyphen		0.0020	B;B;B;B;B;B;B;B;.;.
Vest4		0.48
MutPred		0.46		Loss of catalytic residue at M248 (P = 0.0582);Loss of catalytic residue at M248 (P = 0.0582);Loss of catalytic residue at M248 (P = 0.0582);Loss of catalytic residue at M248 (P = 0.0582);Loss of catalytic residue at M248 (P = 0.0582);Loss of catalytic residue at M248 (P = 0.0582);Loss of catalytic residue at M248 (P = 0.0582);Loss of catalytic residue at M248 (P = 0.0582);Loss of catalytic residue at M248 (P = 0.0582);.;
MVP		0.64
MPC		1.2
ClinPred		0.73	D
GERP RS		5.7
Varity_R		0.34
gMVP		0.66

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: chr3-52682437;