chr22-23787170-A-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_003073.5(SMARCB1):c.1A>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
SMARCB1
NM_003073.5 start_lost
NM_003073.5 start_lost
Scores
5
3
6
Clinical Significance
Conservation
PhyloP100: 2.92
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.1A>C | p.Met1? | start_lost | 1/9 | ENST00000644036.2 | |
SMARCB1 | NM_001362877.2 | c.1A>C | p.Met1? | start_lost | 1/9 | ||
SMARCB1 | NM_001317946.2 | c.1A>C | p.Met1? | start_lost | 1/9 | ||
SMARCB1 | NM_001007468.3 | c.1A>C | p.Met1? | start_lost | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.1A>C | p.Met1? | start_lost | 1/9 | NM_003073.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome AF: 6.96e-7 AC: 1AN: 1437314Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 716004
GnomAD4 exome
AF:
AC:
1
AN:
1437314
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
716004
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
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 | Nov 03, 2023 | This sequence change affects the initiator methionine of the SMARCB1 mRNA. The next in-frame methionine is located at codon 2, 3, and 4. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with ovarian cancer (PMID: 29625052). 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
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PROVEAN
Benign
N;.;N;N;N;N
REVEL
Uncertain
Sift
Pathogenic
D;.;D;D;D;D
Sift4G
Benign
T;.;T;T;T;T
Polyphen
0.0, 0.17
.;B;B;.;.;B
Vest4
MutPred
Loss of MoRF binding (P = 0.0683);Loss of MoRF binding (P = 0.0683);Loss of MoRF binding (P = 0.0683);Loss of MoRF binding (P = 0.0683);Loss of MoRF binding (P = 0.0683);Loss of MoRF binding (P = 0.0683);
MVP
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.