3-50270208-G-A
Position:
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 (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SEMA3B
NM_001290060.2 missense
NM_001290060.2 missense
Scores
9
4
Clinical Significance
Conservation
PhyloP100: 2.86
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 |
---|---|---|---|---|---|---|---|
SEMA3B | NM_001290060.2 | c.191G>A | p.Arg64His | missense_variant | 2/17 | ENST00000616701.5 | |
SEMA3B | NM_001290061.1 | c.191G>A | p.Arg64His | missense_variant | 2/17 | ||
SEMA3B | NM_004636.4 | c.191G>A | p.Arg64His | missense_variant | 3/18 | ||
SEMA3B | NM_001005914.3 | c.191G>A | p.Arg64His | missense_variant | 3/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3B | ENST00000616701.5 | c.191G>A | p.Arg64His | missense_variant | 2/17 | 1 | NM_001290060.2 | P5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
3
AN:
152120
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000416 AC: 1AN: 240418Hom.: 0 AF XY: 0.00000765 AC XY: 1AN XY: 130656
GnomAD3 exomes
AF:
AC:
1
AN:
240418
Hom.:
AF XY:
AC XY:
1
AN XY:
130656
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000124 AC: 18AN: 1456526Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 724126
GnomAD4 exome
AF:
AC:
18
AN:
1456526
Hom.:
Cov.:
32
AF XY:
AC XY:
10
AN XY:
724126
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74306
GnomAD4 genome
AF:
AC:
3
AN:
152120
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74306
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
SEMA3B-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 30, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
.;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;T;T;T;T
Polyphen
1.0
.;D;D;.;.
Vest4
0.25, 0.25, 0.25, 0.25
MutPred
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
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at