rs61729608
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_012431.3(SEMA3E):c.1722A>T(p.Gly574=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000898 in 1,613,334 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0049 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 4 hom. )
Consequence
SEMA3E
NM_012431.3 synonymous
NM_012431.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0130
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 7-83386996-T-A is Benign according to our data. Variant chr7-83386996-T-A is described in ClinVar as [Benign]. Clinvar id is 240862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83386996-T-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.013 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00485 (739/152280) while in subpopulation AFR AF= 0.0167 (694/41570). AF 95% confidence interval is 0.0157. There are 6 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 739 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3E | NM_012431.3 | c.1722A>T | p.Gly574= | synonymous_variant | 15/17 | ENST00000643230.2 | |
SEMA3E | NM_001178129.2 | c.1542A>T | p.Gly514= | synonymous_variant | 15/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3E | ENST00000643230.2 | c.1722A>T | p.Gly574= | synonymous_variant | 15/17 | NM_012431.3 | P1 | ||
SEMA3E | ENST00000642232.1 | c.1722A>T | p.Gly574= | synonymous_variant | 15/17 | ||||
SEMA3E | ENST00000643441.1 | n.1707A>T | non_coding_transcript_exon_variant | 15/17 |
Frequencies
GnomAD3 genomes ? AF: 0.00486 AC: 739AN: 152162Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00121 AC: 302AN: 250568Hom.: 3 AF XY: 0.000908 AC XY: 123AN XY: 135466
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GnomAD4 exome AF: 0.000486 AC: 710AN: 1461054Hom.: 4 Cov.: 30 AF XY: 0.000428 AC XY: 311AN XY: 726814
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GnomAD4 genome ? AF: 0.00485 AC: 739AN: 152280Hom.: 6 Cov.: 32 AF XY: 0.00461 AC XY: 343AN XY: 74466
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 12, 2020 | - - |
CHARGE association Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at