Variant 3-52634806-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001405608.1(PBRM1):c.-41A>C variant causes a 5 prime UTR premature start codon gain 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PBRM1
NM_001405608.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.84

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4005952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
PBRM1	NM_001405608.1 link	c.-41A>C	5_prime_UTR_premature_start_codon_gain_variant	10/27	NP_001392537.1
PBRM1	NM_001405625.1 link	c.-486A>C	5_prime_UTR_premature_start_codon_gain_variant	11/30	NP_001392554.1
PBRM1	NM_001405596.1 link	c.-886A>C	5_prime_UTR_premature_start_codon_gain_variant	12/31	NP_001392525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1 link	c.1097A>C	p.Tyr366Ser	missense_variant	12/32			ENSP00000516722.1		A0A9L9PXL4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250508

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135382

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 SAS exome

AF:

0.0000327

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Benign

0.95

DEOGEN2

Benign

0.24

.;.;T;.;.;.;.;.;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.40

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L;L;L;L;L;L;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.4

N;N;N;N;N;N;N;N;D;D

REVEL

Benign

0.25

Sift

Benign

0.41

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.36

T;T;T;T;T;T;T;T;.;.

Polyphen

1.0

D;D;D;D;D;D;D;D;.;.

Vest4

0.56

MutPred

0.34

.;Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over