rs1949972
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_006379.5(SEMA3C):āc.2028A>Gā(p.Pro676=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 1,613,868 control chromosomes in the GnomAD database, including 759,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.90 ( 63026 hom., cov: 31)
Exomes š: 0.97 ( 696513 hom. )
Consequence
SEMA3C
NM_006379.5 synonymous
NM_006379.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.930
Genes affected
SEMA3C (HGNC:10725): (semaphorin 3C) This gene encodes a secreted glycoprotein that belongs to the semaphorin class 3 family of neuronal guidance cues. The encoded protein contains an N-terminal sema domain, integrin and immunoglobulin-like domains, and a C-terminal basic domain. Homodimerization and proteolytic cleavage of the C-terminal propeptide are necessary for the function of the encoded protein. It binds a neuropilin co-receptor before forming a heterotrimeric complex with an associated plexin. An increase in the expression of this gene correlates with an increase in cancer cell invasion and adhesion. Naturally occurring mutations in this gene are associated with Hirschsprung disease. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 7-80745122-T-C is Benign according to our data. Variant chr7-80745122-T-C is described in ClinVar as [Benign]. Clinvar id is 3058982.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.93 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3C | NM_006379.5 | c.2028A>G | p.Pro676= | synonymous_variant | 18/18 | ENST00000265361.8 | |
SEMA3C | NM_001350120.2 | c.2082A>G | p.Pro694= | synonymous_variant | 18/18 | ||
SEMA3C | NM_001350121.2 | c.1854A>G | p.Pro618= | synonymous_variant | 19/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3C | ENST00000265361.8 | c.2028A>G | p.Pro676= | synonymous_variant | 18/18 | 1 | NM_006379.5 | P1 | |
SEMA3C | ENST00000419255.6 | c.2028A>G | p.Pro676= | synonymous_variant | 18/18 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.903 AC: 137165AN: 151974Hom.: 63008 Cov.: 31
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GnomAD3 exomes AF: 0.940 AC: 236083AN: 251206Hom.: 111829 AF XY: 0.947 AC XY: 128537AN XY: 135756
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GnomAD4 exome AF: 0.975 AC: 1424585AN: 1461776Hom.: 696513 Cov.: 61 AF XY: 0.975 AC XY: 708913AN XY: 727196
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GnomAD4 genome ? AF: 0.902 AC: 137233AN: 152092Hom.: 63026 Cov.: 31 AF XY: 0.903 AC XY: 67097AN XY: 74326
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SEMA3C-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 19, 2022 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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