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GeneBe

3-122912201-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001031702.4(SEMA5B):c.2867A>G(p.Glu956Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SEMA5B
NM_001031702.4 missense

Scores

5
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA5BNM_001031702.4 linkuse as main transcriptc.2867A>G p.Glu956Gly missense_variant 19/23 ENST00000357599.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA5BENST00000357599.8 linkuse as main transcriptc.2867A>G p.Glu956Gly missense_variant 19/231 NM_001031702.4 Q9P283-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000189

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 GeneticsDec 03, 2021The c.2867A>G (p.E956G) alteration is located in exon 19 (coding exon 18) of the SEMA5B gene. This alteration results from a A to G substitution at nucleotide position 2867, causing the glutamic acid (E) at amino acid position 956 to be replaced by a glycine (G). 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
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
Cadd
Pathogenic
34
Dann
Pathogenic
1.0
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D;D;D;D;.;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.78
D;D;D;D;D;D;D
MetaSVM
Benign
-0.68
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.71
T
Polyphen
0.97
.;.;D;.;D;.;.
Vest4
0.82, 0.76, 0.59, 0.79
MutPred
0.59
.;.;Gain of glycosylation at T954 (P = 0.0491);.;Gain of glycosylation at T954 (P = 0.0491);.;Gain of glycosylation at T954 (P = 0.0491);
MVP
0.88
MPC
0.76
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.48
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.34
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.34
Position offset: -29

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: rs1023882353; hg19: chr3-122631048; API