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GeneBe

3-50270208-G-A

Variant summary

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

The NM_001290060.2(SEMA3B):c.191G>A(p.Arg64His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,608,646 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SEMA3B
NM_001290060.2 missense

Scores

9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86
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.191G>A p.Arg64His missense_variant 2/17 ENST00000616701.5
SEMA3BNM_001290061.1 linkuse as main transcriptc.191G>A p.Arg64His missense_variant 2/17
SEMA3BNM_004636.4 linkuse as main transcriptc.191G>A p.Arg64His missense_variant 3/18
SEMA3BNM_001005914.3 linkuse as main transcriptc.191G>A p.Arg64His missense_variant 3/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA3BENST00000616701.5 linkuse as main transcriptc.191G>A p.Arg64His missense_variant 2/171 NM_001290060.2 P5Q13214-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152120
Hom.:
0
Cov.:
33
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000416
AC:
1
AN:
240418
Hom.:
0
AF XY:
0.00000765
AC XY:
1
AN XY:
130656
show subpopulations
Gnomad AFR exome
AF:
0.0000696
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
0.0000124
AC:
18
AN:
1456526
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
724126
show subpopulations
Gnomad4 AFR exome
AF:
0.000180
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:
0.00000991
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152120
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

SEMA3B-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 30, 2023The SEMA3B c.191G>A variant is predicted to result in the amino acid substitution p.Arg64His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
Cadd
Pathogenic
27
Dann
Benign
0.94
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.92
D;D;.;D;D
MetaRNN
Uncertain
0.44
T;T;T;T;T
MetaSVM
Benign
-0.30
T
PrimateAI
Uncertain
0.54
T
Sift4G
Uncertain
0.0040
D;T;T;T;T
Polyphen
1.0
.;D;D;.;.
Vest4
0.25, 0.25, 0.25, 0.25
MutPred
0.53
Gain of methylation at R66 (P = 0.1453);Gain of methylation at R66 (P = 0.1453);Gain of methylation at R66 (P = 0.1453);Gain of methylation at R66 (P = 0.1453);Gain of methylation at R66 (P = 0.1453);
MVP
0.34
ClinPred
0.90
D
GERP RS
4.2
Varity_R
0.15
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs923242762; hg19: chr3-50307639; API