10-110567835-AGGCCTTCG-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005445.4(SMC3):c.15+5_15+12delGGCCTTCG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,154 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005445.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMC3 | ENST00000361804.5 | c.15+5_15+12delGGCCTTCG | splice_region_variant, intron_variant | Intron 1 of 28 | 1 | NM_005445.4 | ENSP00000354720.5 | |||
SMC3 | ENST00000684988.1 | n.148+5_148+12delGGCCTTCG | splice_region_variant, intron_variant | Intron 1 of 24 | ||||||
SMC3 | ENST00000691297.1 | n.148+5_148+12delGGCCTTCG | splice_region_variant, intron_variant | Intron 1 of 16 | ||||||
SMC3 | ENST00000691527.1 | n.105+5_105+12delGGCCTTCG | splice_region_variant, intron_variant | Intron 1 of 15 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247410Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134420
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461154Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726916
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Cornelia de Lange syndrome 3 Uncertain:1
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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with SMC3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change falls in intron 1 of the SMC3 gene. It does not directly change the encoded amino acid sequence of the SMC3 protein. It affects a nucleotide within the consensus splice site. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at