chr7-84999747-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001384900.1(SEMA3D):c.2027T>C(p.Ile676Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,613,904 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 5 hom. )
Consequence
SEMA3D
NM_001384900.1 missense
NM_001384900.1 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 8.61
Genes affected
SEMA3D (HGNC:10726): (semaphorin 3D) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.066411674).
BP6
?
Variant 7-84999747-A-G is Benign according to our data. Variant chr7-84999747-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2636517.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3D | NM_001384900.1 | c.2027T>C | p.Ile676Thr | missense_variant | 19/19 | ENST00000284136.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3D | ENST00000284136.11 | c.2027T>C | p.Ile676Thr | missense_variant | 19/19 | 5 | NM_001384900.1 | P1 | |
SEMA3D | ENST00000484038.1 | n.1153T>C | non_coding_transcript_exon_variant | 10/10 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000815 AC: 124AN: 152110Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000513 AC: 129AN: 251294Hom.: 0 AF XY: 0.000479 AC XY: 65AN XY: 135818
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GnomAD4 exome AF: 0.00130 AC: 1894AN: 1461794Hom.: 5 Cov.: 33 AF XY: 0.00122 AC XY: 886AN XY: 727190
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
SEMA3D-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2023 | The SEMA3D c.2027T>C variant is predicted to result in the amino acid substitution p.Ile676Thr. This variant was reported in an individual with Hirschsprung disease (Jiang et al. 2015. PubMed ID: 25839327). This variant is reported in 0.10% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which may be too common to be the 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | SEMA3D: BP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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