rs2071203

Variant summary

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

The NM_001290060.2(SEMA3B):​c.1244C>A​(p.Thr415Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SEMA3B
NM_001290060.2 missense

Scores

1
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08489624).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SEMA3BNM_001290060.2 linkuse as main transcriptc.1244C>A p.Thr415Asn missense_variant 11/17 ENST00000616701.5 NP_001276989.1 Q13214-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SEMA3BENST00000616701.5 linkuse as main transcriptc.1244C>A p.Thr415Asn missense_variant 11/171 NM_001290060.2 ENSP00000484146.1 Q13214-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1397960
Hom.:
0
Cov.:
31
AF XY:
0.00000145
AC XY:
1
AN XY:
690542
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.24e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.056
T;T;.;.;T;T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.056
N
LIST_S2
Benign
0.30
T;.;T;T;.;T
MetaRNN
Benign
0.085
T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
PrimateAI
Benign
0.26
T
Sift4G
Benign
0.16
T;T;T;T;T;T
Polyphen
0.0070
B;B;B;.;.;.
Vest4
0.047
MutPred
0.57
Loss of phosphorylation at T415 (P = 0.0497);Loss of phosphorylation at T415 (P = 0.0497);.;.;.;.;
MVP
0.18
ClinPred
0.28
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.035
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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: rs2071203; hg19: chr3-50311900; API