3-52648421-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_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
• Clinical Significance: not provided no classification provided O:1
• 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]

ACMG classification

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 exomes AF: 0.00000806 AC: 2 AN: 248108 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134054

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad SAS 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: 6.90e-7 AC: 1 AN: 1449866 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 721794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
Cadd	Uncertain	24
Dann	Benign	0.93
Eigen	Benign	-0.27
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N;N;N;N;N;N;N;N;.;.
MutationTaster	Benign	0.99	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.73	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.070
Sift	Benign	0.93	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.59	T;T;T;T;T;T;T;T;.;.
Polyphen		0.0	B;B;B;B;B;B;B;B;.;.
Vest4		0.23
MutPred		0.42		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		0.39
MPC		0.80
ClinPred		0.44	T
GERP RS		5.7
Varity_R		0.23
gMVP		0.45

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

Other links and lift over

dbSNP: rs587778593; hg19: chr3-52682437;