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GeneBe

3-50269301-C-G

Variant summary

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

The NM_001290060.2(SEMA3B):c.61C>G(p.Leu21Val) 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. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L21L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

SEMA3B
NM_001290060.2 missense

Scores

3
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21
Variant links:
Genes affected
SEMA3B (HGNC:10724): (semaphorin 3B) The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

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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=0.20643666).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA3BNM_001290060.2 linkuse as main transcriptc.61C>G p.Leu21Val missense_variant 1/17 ENST00000616701.5
SEMA3BNM_001290061.1 linkuse as main transcriptc.61C>G p.Leu21Val missense_variant 1/17
SEMA3BNM_004636.4 linkuse as main transcriptc.61C>G p.Leu21Val missense_variant 2/18
SEMA3BNM_001005914.3 linkuse as main transcriptc.61C>G p.Leu21Val missense_variant 2/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA3BENST00000616701.5 linkuse as main transcriptc.61C>G p.Leu21Val missense_variant 1/171 NM_001290060.2 P5Q13214-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 GeneticsSep 30, 2021The c.61C>G (p.L21V) alteration is located in exon 2 (coding exon 1) of the SEMA3B gene. This alteration results from a C to G substitution at nucleotide position 61, causing the leucine (L) at amino acid position 21 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
0.075
BayesDel_addAF
Uncertain
0.018
T
BayesDel_noAF
Benign
-0.21
Cadd
Benign
19
Dann
Benign
0.82
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.59
T;T;.;T;T
MetaRNN
Benign
0.21
T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.66
T
Sift4G
Benign
0.44
T;T;T;T;T
Polyphen
0.038
.;B;B;.;.
Vest4
0.18, 0.17, 0.19, 0.30
MutPred
0.38
Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP
0.19
ClinPred
0.91
D
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.077
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr3-50306733; API