3-52563417-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001405601.1(PBRM1):​c.3997G>A​(p.Glu1333Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1333D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

PBRM1
NM_001405601.1 missense

Scores

3
4
12

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.84
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]
UQCC5 (HGNC:37257): (ubiquinol-cytochrome c reductase complex assembly factor 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24714112).
BP6
Variant 3-52563417-C-T is Benign according to our data. Variant chr3-52563417-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3764511.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PBRM1NM_001405601.1 linkc.3997G>A p.Glu1333Lys missense_variant Exon 26 of 32 NP_001392530.1
PBRM1NM_001405607.1 linkc.3997G>A p.Glu1333Lys missense_variant Exon 26 of 32 NP_001392536.1
PBRM1NM_001405598.1 linkc.3979G>A p.Glu1327Lys missense_variant Exon 25 of 31 NP_001392527.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PBRM1ENST00000707071.1 linkc.3997G>A p.Glu1333Lys missense_variant Exon 26 of 32 ENSP00000516722.1 A0A9L9PXL4

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152114
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000597
AC:
15
AN:
251462
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000116
AC:
169
AN:
1461716
Hom.:
0
Cov.:
31
AF XY:
0.0000976
AC XY:
71
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000133
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
152114
Hom.:
0
Cov.:
31
AF XY:
0.000148
AC XY:
11
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000146
Hom.:
0
Bravo
AF:
0.000121
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary cancer Benign:1
Feb 04, 2025
Mendelics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following: it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease, and/or has normal protein function, and/or has lack of segregation with disease, and/or has been detected in co-occurrence with known pathogenic variant, and/or has lack of disease association in case-control studies, and/or is located in a region inconsistent with a known cause of pathogenicity. GnomAD Frequencey 0.0001184 /0 Homozygotes. Variant with frequency in internal controls -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
.;.;T;.;.;.;.;.;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.25
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
.;.;L;L;L;.;.;.;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.2
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.23
T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.34
T;D;T;T;T;T;T;T;.
Polyphen
0.77
P;P;P;P;P;P;P;P;.
Vest4
0.32
MVP
0.50
MPC
1.1
ClinPred
0.30
T
GERP RS
5.6
Varity_R
0.16
gMVP
0.32

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.

Other links and lift over

dbSNP: rs199643728; hg19: chr3-52597433; COSMIC: COSV99970548; COSMIC: COSV99970548; API