rs201281088
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005445.4(SMC3):c.2644+6T>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000567 in 1,603,786 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0033 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 3 hom. )
Consequence
SMC3
NM_005445.4 splice_donor_region, intron
NM_005445.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.1314
2
Clinical Significance
Conservation
PhyloP100: 2.59
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 10-110601136-T-A is Benign according to our data. Variant chr10-110601136-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 159981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-110601136-T-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00334 (508/152318) while in subpopulation AFR AF= 0.0114 (473/41572). AF 95% confidence interval is 0.0105. There are 3 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 508 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC3 | NM_005445.4 | c.2644+6T>A | splice_donor_region_variant, intron_variant | ENST00000361804.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC3 | ENST00000361804.5 | c.2644+6T>A | splice_donor_region_variant, intron_variant | 1 | NM_005445.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00334 AC: 508AN: 152200Hom.: 3 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000866 AC: 217AN: 250532Hom.: 1 AF XY: 0.000605 AC XY: 82AN XY: 135550
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GnomAD4 exome AF: 0.000277 AC: 402AN: 1451468Hom.: 3 Cov.: 27 AF XY: 0.000214 AC XY: 155AN XY: 722754
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GnomAD4 genome ? AF: 0.00334 AC: 508AN: 152318Hom.: 3 Cov.: 32 AF XY: 0.00303 AC XY: 226AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 07, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 24, 2017 | - - |
Cornelia de Lange syndrome 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 13, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 19, 2014 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at