7-85012788-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001384900.1(SEMA3D):c.1762G>A(p.Glu588Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000028 in 1,609,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
SEMA3D
NM_001384900.1 missense
NM_001384900.1 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 4.00
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21028998).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3D | NM_001384900.1 | c.1762G>A | p.Glu588Lys | missense_variant | 17/19 | ENST00000284136.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3D | ENST00000284136.11 | c.1762G>A | p.Glu588Lys | missense_variant | 17/19 | 5 | NM_001384900.1 | P1 | |
SEMA3D | ENST00000484038.1 | n.888G>A | non_coding_transcript_exon_variant | 8/10 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151760Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250360Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135308
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GnomAD4 exome AF: 0.0000268 AC: 39AN: 1457372Hom.: 0 Cov.: 29 AF XY: 0.0000207 AC XY: 15AN XY: 725178
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151760Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74096
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | The c.1762G>A (p.E588K) alteration is located in exon 15 (coding exon 15) of the SEMA3D gene. This alteration results from a G to A substitution at nucleotide position 1762, causing the glutamic acid (E) at amino acid position 588 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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