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GeneBe

3-122910904-T-C

Variant summary

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

The NM_001031702.4(SEMA5B):c.3233A>G(p.Asn1078Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,650 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: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEMA5B
NM_001031702.4 missense

Scores

2
4
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28
Variant links:
Genes affected
SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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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=0.22819018).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA5BNM_001031702.4 linkuse as main transcriptc.3233A>G p.Asn1078Ser missense_variant 22/23 ENST00000357599.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA5BENST00000357599.8 linkuse as main transcriptc.3233A>G p.Asn1078Ser missense_variant 22/231 NM_001031702.4 Q9P283-1

Frequencies

GnomAD3 genomes
AF:
0.0000265
AC:
4
AN:
151198
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000582
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251468
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000489
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461452
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
727028
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000265
AC:
4
AN:
151198
Hom.:
0
Cov.:
31
AF XY:
0.0000136
AC XY:
1
AN XY:
73732
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000582
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567
ExAC
AF:
0.0000165
AC:
2

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 GeneticsMay 17, 2023The c.3233A>G (p.N1078S) alteration is located in exon 22 (coding exon 21) of the SEMA5B gene. This alteration results from a A to G substitution at nucleotide position 3233, causing the asparagine (N) at amino acid position 1078 to be replaced by a serine (S). 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
0.092
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.44
Cadd
Uncertain
25
Dann
Uncertain
1.0
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D;D;.;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.23
T;T;T;T;T;T;T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.72
T
Polyphen
0.80
.;.;P;.;P;.;.
Vest4
0.82, 0.80, 0.82, 0.82
MutPred
0.66
.;.;Loss of glycosylation at K1083 (P = 0.0424);.;Loss of glycosylation at K1083 (P = 0.0424);.;Loss of glycosylation at K1083 (P = 0.0424);
MVP
0.73
MPC
0.83
ClinPred
0.27
T
GERP RS
4.9
Varity_R
0.17
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs749062365; hg19: chr3-122629751; COSMIC: COSV105853069; API