chr22-23787177-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_003073.5(SMARCB1):c.8T>A(p.Met3Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Consequence
SMARCB1
NM_003073.5 missense
NM_003073.5 missense
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 1.80
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a region_of_interest DNA-binding (size 112) in uniprot entity SNF5_HUMAN there are 13 pathogenic changes around while only 2 benign (87%) in NM_003073.5
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SMARCB1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3033847).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.8T>A | p.Met3Lys | missense_variant | 1/9 | ENST00000644036.2 | |
SMARCB1 | NM_001362877.2 | c.8T>A | p.Met3Lys | missense_variant | 1/9 | ||
SMARCB1 | NM_001317946.2 | c.8T>A | p.Met3Lys | missense_variant | 1/9 | ||
SMARCB1 | NM_001007468.3 | c.8T>A | p.Met3Lys | missense_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.8T>A | p.Met3Lys | missense_variant | 1/9 | NM_003073.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 28, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 3 of the SMARCB1 protein (p.Met3Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCB1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D
Sift4G
Benign
T;.;D;T;D;T
Polyphen
0.0080, 0.0040, 0.72
.;B;B;.;.;P
Vest4
MutPred
Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP
MPC
1.9
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.