chr7-83400091-G-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_012431.3(SEMA3E):āc.1303C>Gā(p.Gln435Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
SEMA3E
NM_012431.3 missense
NM_012431.3 missense
Scores
4
7
7
Clinical Significance
Conservation
PhyloP100: 6.59
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3E | NM_012431.3 | c.1303C>G | p.Gln435Glu | missense_variant | 11/17 | ENST00000643230.2 | |
SEMA3E | NM_001178129.2 | c.1123C>G | p.Gln375Glu | missense_variant | 11/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3E | ENST00000643230.2 | c.1303C>G | p.Gln435Glu | missense_variant | 11/17 | NM_012431.3 | P1 | ||
SEMA3E | ENST00000642232.1 | c.1303C>G | p.Gln435Glu | missense_variant | 11/17 | ||||
SEMA3E | ENST00000643441.1 | n.1288C>G | non_coding_transcript_exon_variant | 11/17 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152088Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251258Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135786
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461776Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727172
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152088Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74288
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CHARGE syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2022 | This variant is present in population databases (rs752774852, gnomAD 0.01%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 435 of the SEMA3E protein (p.Gln435Glu). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SEMA3E protein function. ClinVar contains an entry for this variant (Variation ID: 529115). - |
SEMA3E-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 08, 2024 | The SEMA3E c.1303C>G variant is predicted to result in the amino acid substitution p.Gln435Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.014% of alleles in individuals of Latino descent in gnomAD, which may be too common to be a primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;H;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;.
Sift4G
Uncertain
D;.;D;.
Polyphen
D;D;.;.
Vest4
MutPred
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at