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GeneBe

5-116446708-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020796.5(SEMA6A):c.2998C>G(p.Leu1000Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SEMA6A
NM_020796.5 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.611
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.082957566).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6ANM_020796.5 linkuse as main transcriptc.2998C>G p.Leu1000Val missense_variant 19/19 ENST00000343348.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6AENST00000343348.11 linkuse as main transcriptc.2998C>G p.Leu1000Val missense_variant 19/191 NM_020796.5 P4Q9H2E6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsAug 08, 2022The c.2998C>G (p.L1000V) alteration is located in exon 19 (coding exon 18) of the SEMA6A gene. This alteration results from a C to G substitution at nucleotide position 2998, causing the leucine (L) at amino acid position 1000 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
Cadd
Benign
17
Dann
Benign
0.95
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.66
D
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.083
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.74
D;D;D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.59
N;N;N;N;N
REVEL
Benign
0.052
Sift
Benign
0.28
T;T;T;T;T
Sift4G
Benign
0.80
T;T;T;T;T
Polyphen
0.0020, 0.0010
.;.;B;B;.
Vest4
0.053
MutPred
0.10
Loss of stability (P = 0.0777);.;.;.;Loss of stability (P = 0.0777);
MVP
0.17
MPC
0.20
ClinPred
0.22
T
GERP RS
3.5
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-115782404; API