rs61729612

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R208R) has been classified as Likely 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

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Kallmann syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
CHARGE syndrome
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

SEMA3E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3 link	c.623G>C	p.Arg208Pro	missense_variant	Exon 6 of 17	ENST00000643230.2	NP_036563.1	O15041-1
SEMA3E	NM_001178129.2 link	c.443G>C	p.Arg148Pro	missense_variant	Exon 6 of 17		NP_001171600.1	O15041-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2 link	c.623G>C	p.Arg208Pro	missense_variant	Exon 6 of 17		NM_012431.3	ENSP00000496491.1		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

GnomAD2 exomes

AF:

0.117

AC:

29289

AN:

250778

AF XY:

0.116

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 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

African (AFR)

AF:

0.0753

AC:

2521

AN:

33466

American (AMR)

AF:

0.123

AC:

5505

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

6194

AN:

26130

East Asian (EAS)

AF:

0.166

AC:

6606

AN:

39678

South Asian (SAS)

AF:

0.0662

AC:

5711

AN:

86250

European-Finnish (FIN)

AF:

0.110

AC:

5888

AN:

53386

Middle Eastern (MID)

AF:

0.152

AC:

876

AN:

5766

European-Non Finnish (NFE)

AF:

0.120

AC:

133124

AN:

1111576

Other (OTH)

AF:

0.124

AC:

7467

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

7681

15362

23042

30723

38404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4820

9640

14460

19280

24100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.110

AC:

16777

AN:

152216

Hom.:

985

Cov.:

AF XY:

0.111

AC XY:

8257

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0770

AC:

3197

AN:

41538

American (AMR)

AF:

0.119

AC:

1812

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

848

AN:

3472

East Asian (EAS)

AF:

0.146

AC:

754

AN:

5154

South Asian (SAS)

AF:

0.0654

AC:

316

AN:

4832

European-Finnish (FIN)

AF:

0.105

AC:

1117

AN:

10602

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8334

AN:

68024

Other (OTH)

AF:

0.118

AC:

250

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

783

1565

2348

3130

3913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Aug 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.;.

PhyloP100

0.68

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over