rs587778593

Variant names:

• chr3-52648421-G-A
• rs587778593
• NM_001405607.1:c.736C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-52648421-G-A
• chr3-52648421-G-C
• chr3-52648421-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001405607.1(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 NM_001405607.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27084702).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	NM_001405607.1	MANE Select	c.736C>T	p.His246Tyr	missense	Exon 8 of 32	NP_001392536.1
	PBRM1	NM_001405601.1		c.736C>T	p.His246Tyr	missense	Exon 8 of 32	NP_001392530.1
	PBRM1	NM_001405598.1		c.763C>T	p.His255Tyr	missense	Exon 8 of 31	NP_001392527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	ENST00000707071.1	MANE Select	c.736C>T	p.His246Tyr	missense	Exon 8 of 32	ENSP00000516722.1
	PBRM1	ENST00000296302.11	TSL:1	c.736C>T	p.His246Tyr	missense	Exon 7 of 30	ENSP00000296302.7
	PBRM1	ENST00000409114.7	TSL:1	c.736C>T	p.His246Tyr	missense	Exon 7 of 30	ENSP00000386643.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.075	N
PhyloP100		4.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.075
Sift	Benign	0.055	T
Sift4G	Uncertain	0.054	T
Polyphen		0.17	B
Vest4		0.33
MutPred		0.47		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
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs587778593; hg19: chr3-52682437;