7-83367594-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_012431.3(SEMA3E):c.2320G>T(p.Asp774Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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.2320G>T | p.Asp774Tyr | missense_variant | 17/17 | ENST00000643230.2 | |
SEMA3E | NM_001178129.2 | c.2140G>T | p.Asp714Tyr | missense_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3E | ENST00000643230.2 | c.2320G>T | p.Asp774Tyr | missense_variant | 17/17 | NM_012431.3 | P1 | ||
SEMA3E | ENST00000643441.1 | n.2305G>T | non_coding_transcript_exon_variant | 17/17 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461824Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727216
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74300
ClinVar
Submissions by phenotype
CHARGE syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2023 | This variant has not been reported in the literature in individuals affected with SEMA3E-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 529136). This variant is present in population databases (rs767621375, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 774 of the SEMA3E protein (p.Asp774Tyr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at