rs1555877287
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP2PP3_ModeratePP5
The NM_003073.5(SMARCB1):c.602G>A(p.Arg201Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 34)
Consequence
SMARCB1
NM_003073.5 missense
NM_003073.5 missense
Scores
9
5
2
Clinical Significance
Conservation
PhyloP100: 9.96
Genes affected
SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SMARCB1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.934
PP5
?
Variant 22-23803396-G-A is Pathogenic according to our data. Variant chr22-23803396-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438304.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.602G>A | p.Arg201Gln | missense_variant | 5/9 | ENST00000644036.2 | |
SMARCB1 | NM_001362877.2 | c.656G>A | p.Arg219Gln | missense_variant | 5/9 | ||
SMARCB1 | NM_001317946.2 | c.629G>A | p.Arg210Gln | missense_variant | 5/9 | ||
SMARCB1 | NM_001007468.3 | c.575G>A | p.Arg192Gln | missense_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.602G>A | p.Arg201Gln | missense_variant | 5/9 | NM_003073.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
Alfa
AF:
Hom.:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 15 Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals | Nov 01, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;D;N;.;D
REVEL
Pathogenic
Sift
Benign
D;.;D;D;.;D
Sift4G
Uncertain
D;.;D;.;.;D
Polyphen
0.58, 0.87
.;P;P;.;.;.
Vest4
MutPred
0.83
.;.;Gain of ubiquitination at K208 (P = 0.0882);.;.;.;
MVP
MPC
2.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at