rs1880959
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1
The ENST00000265361.8(SEMA3C):c.1044G>T(p.Val348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 1,605,138 control chromosomes in the GnomAD database, including 6,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.080 ( 503 hom., cov: 32)
Exomes 𝑓: 0.086 ( 5828 hom. )
Consequence
SEMA3C
ENST00000265361.8 synonymous
ENST00000265361.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.128
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.19).
BP6
Variant 7-80798179-C-A is Benign according to our data. Variant chr7-80798179-C-A is described in ClinVar as [Benign]. Clinvar id is 3059373.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.128 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEMA3C | NM_006379.5 | c.1044G>T | p.Val348= | synonymous_variant | 11/18 | ENST00000265361.8 | NP_006370.1 | |
SEMA3C | NM_001350120.2 | c.1098G>T | p.Val366= | synonymous_variant | 11/18 | NP_001337049.1 | ||
SEMA3C | NM_001350121.2 | c.870G>T | p.Val290= | synonymous_variant | 12/19 | NP_001337050.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SEMA3C | ENST00000265361.8 | c.1044G>T | p.Val348= | synonymous_variant | 11/18 | 1 | NM_006379.5 | ENSP00000265361 | P1 | |
SEMA3C | ENST00000419255.6 | c.1044G>T | p.Val348= | synonymous_variant | 11/18 | 2 | ENSP00000411193 | P1 | ||
SEMA3C | ENST00000475955.1 | n.60G>T | non_coding_transcript_exon_variant | 1/2 | 4 | |||||
SEMA3C | ENST00000458729.5 | c.*577G>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/9 | 2 | ENSP00000393825 |
Frequencies
GnomAD3 genomes AF: 0.0795 AC: 12086AN: 151996Hom.: 501 Cov.: 32
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GnomAD3 exomes AF: 0.0658 AC: 15852AN: 240870Hom.: 669 AF XY: 0.0661 AC XY: 8626AN XY: 130544
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GnomAD4 exome AF: 0.0858 AC: 124692AN: 1453026Hom.: 5828 Cov.: 31 AF XY: 0.0841 AC XY: 60782AN XY: 722816
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GnomAD4 genome AF: 0.0795 AC: 12097AN: 152112Hom.: 503 Cov.: 32 AF XY: 0.0761 AC XY: 5662AN XY: 74358
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
SEMA3C-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 03, 2023 | 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