chr10-110567743-C-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005445.4(SMC3):c.-74C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,577,144 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0013 ( 3 hom. )
Consequence
SMC3
NM_005445.4 5_prime_UTR
NM_005445.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.765
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 10-110567743-C-A is Benign according to our data. Variant chr10-110567743-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 298761.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00123 (188/152348) while in subpopulation AMR AF= 0.00333 (51/15310). AF 95% confidence interval is 0.0026. There are 0 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 188 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC3 | NM_005445.4 | c.-74C>A | 5_prime_UTR_variant | 1/29 | ENST00000361804.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC3 | ENST00000361804.5 | c.-74C>A | 5_prime_UTR_variant | 1/29 | 1 | NM_005445.4 | P1 | ||
SMC3 | ENST00000684988.1 | n.60C>A | non_coding_transcript_exon_variant | 1/25 | |||||
SMC3 | ENST00000691297.1 | n.60C>A | non_coding_transcript_exon_variant | 1/17 | |||||
SMC3 | ENST00000691527.1 | n.17C>A | non_coding_transcript_exon_variant | 1/16 |
Frequencies
GnomAD3 genomes AF: 0.00123 AC: 188AN: 152230Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 0.00132 AC: 1885AN: 1424796Hom.: 3 Cov.: 26 AF XY: 0.00135 AC XY: 960AN XY: 710646
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GnomAD4 genome AF: 0.00123 AC: 188AN: 152348Hom.: 0 Cov.: 34 AF XY: 0.00144 AC XY: 107AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cornelia de Lange syndrome 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at