rs587784428
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_005445.4(SMC3):c.548-5_548-4dup variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 1,610,522 control chromosomes in the GnomAD database, including 1,987 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.059 ( 349 hom., cov: 31)
Exomes 𝑓: 0.044 ( 1638 hom. )
Consequence
SMC3
NM_005445.4 splice_region, splice_polypyrimidine_tract, intron
NM_005445.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.55
Genes affected
SMC3 (HGNC:2468): (structural maintenance of chromosomes 3) This gene belongs to the SMC3 subfamily of SMC proteins. The encoded protein occurs in certain cell types as either an intracellular, nuclear protein or a secreted protein. The nuclear form, known as structural maintenance of chromosomes 3, is a component of the multimeric cohesin complex that holds together sister chromatids during mitosis, enabling proper chromosome segregation. Post-translational modification of the encoded protein by the addition of chondroitin sulfate chains gives rise to the secreted proteoglycan bamacan, an abundant basement membrane protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 10-110581915-C-CTT is Benign according to our data. Variant chr10-110581915-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 159989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC3 | NM_005445.4 | c.548-5_548-4dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000361804.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC3 | ENST00000361804.5 | c.548-5_548-4dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005445.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0592 AC: 8995AN: 152064Hom.: 348 Cov.: 31
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GnomAD3 exomes AF: 0.0422 AC: 10565AN: 250438Hom.: 294 AF XY: 0.0424 AC XY: 5748AN XY: 135682
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GnomAD4 exome AF: 0.0442 AC: 64512AN: 1458340Hom.: 1638 Cov.: 31 AF XY: 0.0440 AC XY: 31927AN XY: 725718
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GnomAD4 genome AF: 0.0592 AC: 9007AN: 152182Hom.: 349 Cov.: 31 AF XY: 0.0584 AC XY: 4343AN XY: 74418
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 02, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 02, 2017 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 05, 2019 | 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. - |
Cornelia de Lange syndrome 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
De Lange syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at