rs61729612

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012431.3(SEMA3E):c.623G>C(p.Arg208Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,613,448 control chromosomes in the GnomAD database, including 11,976 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 985 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10991 hom. )

Consequence

SEMA3E
NM_012431.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.678

Variant links:

Genes affected

SEMA3E (HGNC:10727): (semaphorin 3E) Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene encodes a class 3 semaphorin. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

SEMA3E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017450154).

BP6

Variant 7-83408415-C-G is Benign according to our data. Variant chr7-83408415-C-G is described in ClinVar as [Benign]. Clinvar id is 260256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3E	NM_012431.3 linkuse as main transcript	c.623G>C	p.Arg208Pro	missense_variant	6/17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2 linkuse as main transcript	c.443G>C	p.Arg148Pro	missense_variant	6/17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2 linkuse as main transcript	c.623G>C	p.Arg208Pro	missense_variant	6/17		NM_012431.3	ENSP00000496491	P1	O15041-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16773

AN:

152102

Hom.:

984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0770

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0651

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.119

GnomAD3 exomes

AF:

0.117

AC:

29289

AN:

250778

Hom.:

1924

AF XY:

0.116

AC XY:

15744

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.0739

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.0652

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.119

AC:

173892

AN:

1461232

Hom.:

10991

Cov.:

AF XY:

0.118

AC XY:

85767

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.0753

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.0662

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.110

AC:

16777

AN:

152216

Hom.:

985

Cov.:

AF XY:

0.111

AC XY:

8257

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0770

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.0654

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.129

Hom.:

1066

Bravo

AF:

0.109

TwinsUK

AF:

0.119

AC:

441

ALSPAC

AF:

0.125

AC:

481

ESP6500AA

AF:

0.0785

AC:

346

ESP6500EA

AF:

0.129

AC:

1106

ExAC

AF:

0.113

AC:

13722

Asia WGS

AF:

0.107

AC:

371

AN:

3478

EpiCase

AF:

0.130

EpiControl

AF:

0.134

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CHARGE syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.027

T;T;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.32

.;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

N;N;.;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

0.060

N;.;N;.

REVEL

Benign

0.049

Sift

Benign

0.54

T;.;T;.

Sift4G

Benign

0.45

T;.;T;.

Polyphen

0.0

B;B;.;.

Vest4

0.22

MPC

0.64

ClinPred

0.014

GERP RS

1.9

Varity_R

0.24

gMVP

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over