22-23833701-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_003073.5(SMARCB1):c.1116G>A(p.Thr372Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_003073.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.1116G>A | p.Thr372Thr | splice_region_variant, synonymous_variant | Exon 8 of 9 | ENST00000644036.2 | NP_003064.2 | |
SMARCB1 | NM_001362877.2 | c.1170G>A | p.Thr390Thr | splice_region_variant, synonymous_variant | Exon 8 of 9 | NP_001349806.1 | ||
SMARCB1 | NM_001317946.2 | c.1143G>A | p.Thr381Thr | splice_region_variant, synonymous_variant | Exon 8 of 9 | NP_001304875.1 | ||
SMARCB1 | NM_001007468.3 | c.1089G>A | p.Thr363Thr | splice_region_variant, synonymous_variant | Exon 8 of 9 | NP_001007469.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000342 AC: 86AN: 251260Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135846
GnomAD4 exome AF: 0.000274 AC: 400AN: 1461728Hom.: 1 Cov.: 32 AF XY: 0.000264 AC XY: 192AN XY: 727154
GnomAD4 genome AF: 0.000151 AC: 23AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74456
ClinVar
Submissions by phenotype
not provided Benign:4
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SMARCB1: BP4, BP7, BS1 -
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not specified Benign:1
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Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at