5-116446933-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020796.5(SEMA6A):c.2773C>T(p.Leu925Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,712 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SEMA6A
NM_020796.5 missense
NM_020796.5 missense
Scores
5
11
Clinical Significance
Conservation
PhyloP100: 5.88
Genes affected
SEMA6A (HGNC:10738): (semaphorin 6A) Predicted to enable identical protein binding activity; signaling receptor binding activity; and transmembrane signaling receptor activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be integral component of membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.38591442).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA6A | NM_020796.5 | c.2773C>T | p.Leu925Phe | missense_variant | 19/19 | ENST00000343348.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA6A | ENST00000343348.11 | c.2773C>T | p.Leu925Phe | missense_variant | 19/19 | 1 | NM_020796.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249244Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135220
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461712Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727138
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
Bravo
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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 | Jun 07, 2023 | The c.2773C>T (p.L925F) alteration is located in exon 19 (coding exon 18) of the SEMA6A gene. This alteration results from a C to T substitution at nucleotide position 2773, causing the leucine (L) at amino acid position 925 to be replaced by a phenylalanine (F). 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
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;D;D
Sift4G
Benign
T;T;D;D;T
Polyphen
0.99, 0.99
.;.;D;D;.
Vest4
MutPred
Gain of catalytic residue at L925 (P = 0.0117);.;.;.;Gain of catalytic residue at L925 (P = 0.0117);
MVP
MPC
ClinPred
D
GERP RS
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