7-83367698-CTCTT-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012431.3(SEMA3E):c.2212_2215del(p.Lys738GlyfsTer47) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SEMA3E
NM_012431.3 frameshift
NM_012431.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.05
Genes affected
SEMA3E (HGNC:10727): (semaphorin 3E) Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene encodes a class 3 semaphorin. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3E | NM_012431.3 | c.2212_2215del | p.Lys738GlyfsTer47 | frameshift_variant | 17/17 | ENST00000643230.2 | |
SEMA3E | NM_001178129.2 | c.2032_2035del | p.Lys678GlyfsTer47 | frameshift_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3E | ENST00000643230.2 | c.2212_2215del | p.Lys738GlyfsTer47 | frameshift_variant | 17/17 | NM_012431.3 | P1 | ||
SEMA3E | ENST00000643441.1 | n.2197_2200del | non_coding_transcript_exon_variant | 17/17 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251488Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135920
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461880Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727242
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CHARGE syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with SEMA3E-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change results in a frameshift in the SEMA3E gene (p.Lys738Glyfs*47). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the SEMA3E protein and extend the protein by 8 additional amino acid residues. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at