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GeneBe

3-50159677-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004186.5(SEMA3F):c.55T>C(p.Ser19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,613,256 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S19F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000073 ( 1 hom. )

Consequence

SEMA3F
NM_004186.5 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28
Variant links:
Genes affected
SEMA3F (HGNC:10728): (semaphorin 3F) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin loop and a C-terminal basic domain. This gene is expressed by the endothelial cells where it was found to act in an autocrine fashion to induce apoptosis, inhibit cell proliferation and survival, and function as an anti-tumorigenic agent. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.006094694).
BP6
Variant 3-50159677-T-C is Benign according to our data. Variant chr3-50159677-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3054991.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd at 122 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA3FNM_004186.5 linkuse as main transcriptc.55T>C p.Ser19Pro missense_variant 2/19 ENST00000002829.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA3FENST00000002829.8 linkuse as main transcriptc.55T>C p.Ser19Pro missense_variant 2/191 NM_004186.5 Q13275-1

Frequencies

GnomAD3 genomes
AF:
0.000802
AC:
122
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00287
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000164
AC:
41
AN:
249868
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135342
show subpopulations
Gnomad AFR exome
AF:
0.00236
Gnomad AMR exome
AF:
0.0000292
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000732
AC:
107
AN:
1460932
Hom.:
1
Cov.:
31
AF XY:
0.0000509
AC XY:
37
AN XY:
726784
show subpopulations
Gnomad4 AFR exome
AF:
0.00299
Gnomad4 AMR exome
AF:
0.0000448
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:
0.00000180
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000801
AC:
122
AN:
152324
Hom.:
0
Cov.:
33
AF XY:
0.000792
AC XY:
59
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00286
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000239
Hom.:
0
Bravo
AF:
0.000873
ESP6500AA
AF:
0.00340
AC:
15
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000231
AC:
28

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SEMA3F-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 15, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.38
Cadd
Benign
21
Dann
Benign
0.91
DEOGEN2
Benign
0.013
T;T;T;.;.
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.54
T;T;T;T;T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.0061
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-0.73
N;N;N;N;N
REVEL
Benign
0.14
Sift
Benign
0.27
T;T;T;T;T
Sift4G
Benign
0.23
T;T;T;T;T
Polyphen
0.0
.;.;B;.;.
Vest4
0.33, 0.34
MVP
0.72
MPC
0.30
ClinPred
0.015
T
GERP RS
1.9
Varity_R
0.075
gMVP
0.24

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: rs140721147; hg19: chr3-50197110; API