chr7-83367698-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_012431.3(SEMA3E):c.2216G>A(p.Arg739Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012431.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3E | NM_012431.3 | c.2216G>A | p.Arg739Lys | missense_variant | 17/17 | ENST00000643230.2 | |
SEMA3E | NM_001178129.2 | c.2036G>A | p.Arg679Lys | missense_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3E | ENST00000643230.2 | c.2216G>A | p.Arg739Lys | missense_variant | 17/17 | NM_012431.3 | P1 | ||
SEMA3E | ENST00000643441.1 | n.2201G>A | non_coding_transcript_exon_variant | 17/17 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251488Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135920
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727242
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74266
ClinVar
Submissions by phenotype
CHARGE syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 739 of the SEMA3E protein (p.Arg739Lys). This variant is present in population databases (rs750426538, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SEMA3E-related conditions. ClinVar contains an entry for this variant (Variation ID: 1387125). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at