chr3-52648421-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The ENST00000707071.1(PBRM1):c.736C>A(p.His246Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
PBRM1
ENST00000707071.1 missense
ENST00000707071.1 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 4.58
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]
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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;
PP2
?
Missense variant where missense usually causes diseases, PBRM1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12165326).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PBRM1 | NM_001405607.1 | c.736C>A | p.His246Asn | missense_variant | 8/32 | ENST00000707071.1 | |
PBRM1 | NR_175959.1 | n.913C>A | non_coding_transcript_exon_variant | 8/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PBRM1 | ENST00000707071.1 | c.736C>A | p.His246Asn | missense_variant | 8/32 | NM_001405607.1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248108Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134054
GnomAD3 exomes
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2
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248108
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134054
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GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1449866Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 721794
GnomAD4 exome
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27
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721794
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
2
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;N;N;N;N;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;.;.
Polyphen
B;B;B;B;B;B;B;B;.;.
Vest4
MutPred
Loss of catalytic residue at M248 (P = 0.0592);Loss of catalytic residue at M248 (P = 0.0592);Loss of catalytic residue at M248 (P = 0.0592);Loss of catalytic residue at M248 (P = 0.0592);Loss of catalytic residue at M248 (P = 0.0592);Loss of catalytic residue at M248 (P = 0.0592);Loss of catalytic residue at M248 (P = 0.0592);Loss of catalytic residue at M248 (P = 0.0592);Loss of catalytic residue at M248 (P = 0.0592);.;
MVP
MPC
0.80
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at