chr7-83367599-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_012431.3(SEMA3E):c.2315C>T(p.Thr772Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T772T) has been classified as Likely benign.
Frequency
Consequence
NM_012431.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3E | NM_012431.3 | c.2315C>T | p.Thr772Met | missense_variant | 17/17 | ENST00000643230.2 | |
SEMA3E | NM_001178129.2 | c.2135C>T | p.Thr712Met | missense_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3E | ENST00000643230.2 | c.2315C>T | p.Thr772Met | missense_variant | 17/17 | NM_012431.3 | P1 | ||
SEMA3E | ENST00000643441.1 | n.2300C>T | non_coding_transcript_exon_variant | 17/17 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000596 AC: 15AN: 251492Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135922
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461818Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727202
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
CHARGE syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 08, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 772 of the SEMA3E protein (p.Thr772Met). This variant is present in population databases (rs766002060, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SEMA3E-related conditions. 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