rs587778593

chr3-52648421-G-Achr3-52648421-G-Cchr3-52648421-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The ENST00000707071.1(PBRM1):c.736C>T(p.His246Tyr) 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 2 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=0.27084702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.736C>T	p.His246Tyr	missense_variant	8/32	ENST00000707071.1
PBRM1	NR_175959.1	n.913C>T		non_coding_transcript_exon_variant	8/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.736C>T	p.His246Tyr	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	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.075	N;N;N;N;N;N;N;N;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.075
Sift	Benign	0.055	T;T;T;T;T;T;T;T;T;D
Sift4G	Uncertain	0.054	T;D;T;T;T;D;T;T;.;.
Polyphen		0.17	B;B;P;B;B;B;B;P;.;.
Vest4		0.33
MutPred		0.47		Loss of ubiquitination at K243 (P = 0.0607);Loss of ubiquitination at K243 (P = 0.0607);Loss of ubiquitination at K243 (P = 0.0607);Loss of ubiquitination at K243 (P = 0.0607);Loss of ubiquitination at K243 (P = 0.0607);Loss of ubiquitination at K243 (P = 0.0607);Loss of ubiquitination at K243 (P = 0.0607);Loss of ubiquitination at K243 (P = 0.0607);Loss of ubiquitination at K243 (P = 0.0607);.;
MVP		0.35
MPC		0.85
ClinPred		0.68	D
GERP RS		5.7
Varity_R		0.31
gMVP		0.54

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;