3-52609669-T-G

Variant names:

• chr3-52609669-T-G
• rs3755806
• NM_001405607.1:c.2256A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001405607.1(PBRM1):​c.2256A>C​(p.Thr752Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PBRM1 NM_001405607.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.

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.2256A>C	p.Thr752Thr	synonymous	Exon 18 of 32	NP_001392536.1
	PBRM1	NM_001405601.1		c.2256A>C	p.Thr752Thr	synonymous	Exon 18 of 32	NP_001392530.1
	PBRM1	NM_001405598.1		c.2238A>C	p.Thr746Thr	synonymous	Exon 17 of 31	NP_001392527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	ENST00000707071.1	MANE Select	c.2256A>C	p.Thr752Thr	synonymous	Exon 18 of 32	ENSP00000516722.1
	PBRM1	ENST00000296302.11	TSL:1	c.2211A>C	p.Thr737Thr	synonymous	Exon 16 of 30	ENSP00000296302.7
	PBRM1	ENST00000409114.7	TSL:1	c.2256A>C	p.Thr752Thr	synonymous	Exon 17 of 30	ENSP00000386643.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.68
PhyloP100		-1.3

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: rs3755806; hg19: chr3-52643685;