chr7-80748949-C-T
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_006379.5(SEMA3C):c.1791G>A(p.Pro597=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,613,222 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 2 hom. )
Consequence
SEMA3C
NM_006379.5 synonymous
NM_006379.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.82
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 7-80748949-C-T is Benign according to our data. Variant chr7-80748949-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 733120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.82 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3C | NM_006379.5 | c.1791G>A | p.Pro597= | synonymous_variant | 17/18 | ENST00000265361.8 | |
SEMA3C | NM_001350120.2 | c.1845G>A | p.Pro615= | synonymous_variant | 17/18 | ||
SEMA3C | NM_001350121.2 | c.1617G>A | p.Pro539= | synonymous_variant | 18/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3C | ENST00000265361.8 | c.1791G>A | p.Pro597= | synonymous_variant | 17/18 | 1 | NM_006379.5 | P1 | |
SEMA3C | ENST00000419255.6 | c.1791G>A | p.Pro597= | synonymous_variant | 17/18 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00192 AC: 292AN: 152002Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000487 AC: 122AN: 250668Hom.: 1 AF XY: 0.000376 AC XY: 51AN XY: 135492
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GnomAD4 exome AF: 0.000216 AC: 316AN: 1461102Hom.: 2 Cov.: 33 AF XY: 0.000201 AC XY: 146AN XY: 726888
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GnomAD4 genome AF: 0.00193 AC: 294AN: 152120Hom.: 2 Cov.: 32 AF XY: 0.00176 AC XY: 131AN XY: 74374
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
SEMA3C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 19, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at