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GeneBe

3-50271009-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001290060.2(SEMA3B):c.450G>C(p.Glu150Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000691 in 1,447,458 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: 6.9e-7 ( 0 hom. )

Consequence

SEMA3B
NM_001290060.2 missense, splice_region

Scores

1
11
Splicing: ADA: 0.9861
1
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA3BNM_001290060.2 linkuse as main transcriptc.450G>C p.Glu150Asp missense_variant, splice_region_variant 4/17 ENST00000616701.5
SEMA3BNM_001290061.1 linkuse as main transcriptc.450G>C p.Glu150Asp missense_variant, splice_region_variant 4/17
SEMA3BNM_004636.4 linkuse as main transcriptc.450G>C p.Glu150Asp missense_variant, splice_region_variant 5/18
SEMA3BNM_001005914.3 linkuse as main transcriptc.450G>C p.Glu150Asp missense_variant, splice_region_variant 5/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA3BENST00000616701.5 linkuse as main transcriptc.450G>C p.Glu150Asp missense_variant, splice_region_variant 4/171 NM_001290060.2 P5Q13214-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447458
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
718656
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Neurodevelopmental disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInstitute of Human Genetics, University of Leipzig Medical CenterJan 01, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Benign
-0.25
Cadd
Uncertain
25
Dann
Benign
0.74
Eigen
Benign
-0.049
Eigen_PC
Benign
0.072
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.77
T;T;.;T;T
MetaRNN
Benign
0.24
T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.37
T
Sift4G
Benign
0.074
T;D;D;D;D
Polyphen
0.0
.;B;B;B;.
Vest4
0.25, 0.25, 0.25, 0.25
MutPred
0.49
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP
0.31
ClinPred
0.90
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.19
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
dbscSNV1_RF
Benign
0.67
SpliceAI score (max)
0.50
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.50
Position offset: 0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1701032174; hg19: chr3-50308440; API