Genetic Variant PBRM1:p.Tyr366Ser (chr3-52634806-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001405607.1(PBRM1):c.1097A>C(p.Tyr366Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Y366C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PBRM1
NM_001405607.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.84

Publications

5 publications found

Variant links:

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]

PBRM1 links:

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ACMG classification

Classification was made for transcript

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=0.4005952).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PBRM1	NM_001405607.1	MANE Select	c.1097A>C	p.Tyr366Ser	missense	Exon 12 of 32	NP_001392536.1
PBRM1	NM_001405608.1		c.-41A>C		5_prime_UTR_premature_start_codon_gain	Exon 10 of 27	NP_001392537.1
PBRM1	NM_001405625.1		c.-486A>C		5_prime_UTR_premature_start_codon_gain	Exon 11 of 30	NP_001392554.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PBRM1	ENST00000707071.1	MANE Select	c.1097A>C	p.Tyr366Ser	missense	Exon 12 of 32	ENSP00000516722.1
PBRM1	ENST00000296302.11	TSL:1	c.1097A>C	p.Tyr366Ser	missense	Exon 11 of 30	ENSP00000296302.7
PBRM1	ENST00000409114.7	TSL:1	c.1097A>C	p.Tyr366Ser	missense	Exon 11 of 30	ENSP00000386643.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250508

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460688

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111050

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.020

MetaRNN

Benign

0.40

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

5.8

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.25

Sift

Benign

0.41

Sift4G

Benign

0.36

Polyphen

1.0

Vest4

0.56

MutPred

0.34

Gain of relative solvent accessibility (P = 0.0098)

MVP

0.57

MPC

1.4

ClinPred

0.67

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.67

Mutation Taster

=73/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over