rs142204796

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012431.3(SEMA3E):c.2102G>T(p.Ser701Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00551 in 1,614,098 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 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. S701R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 46 hom. )

Consequence

SEMA3E
NM_012431.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.399

Publications

13 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004215896).

BP6

Variant 7-83367812-C-A is Benign according to our data. Variant chr7-83367812-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 218701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 628 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3 link	c.2102G>T	p.Ser701Ile	missense_variant	Exon 17 of 17	ENST00000643230.2	NP_036563.1	O15041-1
SEMA3E	NM_001178129.2 link	c.1922G>T	p.Ser641Ile	missense_variant	Exon 17 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.2102G>T	p.Ser701Ile	missense_variant	Exon 17 of 17		NM_012431.3	ENSP00000496491.1		O15041-1
SEMA3E	ENST00000643441.1 link	n.2087G>T		non_coding_transcript_exon_variant	Exon 17 of 17

Frequencies

GnomAD3 genomes

AF:

0.00413

AC:

628

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00787

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00516

Gnomad OTH

AF:

0.00624

GnomAD2 exomes

AF:

0.00537

AC:

1350

AN:

251402

AF XY:

0.00561

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00565

AC:

8261

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

4106

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33480

American (AMR)

AF:

0.00280

AC:

125

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

420

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0102

AC:

876

AN:

86258

European-Finnish (FIN)

AF:

0.00163

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00919

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00564

AC:

6269

AN:

1111990

Other (OTH)

AF:

0.00669

AC:

404

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

529

1057

1586

2114

2643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.00412

AC:

628

AN:

152246

Hom.:

Cov.:

AF XY:

0.00412

AC XY:

307

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41568

American (AMR)

AF:

0.00373

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00808

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00515

AC:

350

AN:

68012

Other (OTH)

AF:

0.00617

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00521

Hom.:

Bravo

AF:

0.00420

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00519

AC:

630

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00573

EpiControl

AF:

0.00492

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 31, 2020

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

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SEMA3E: BP4, BS1, BS2 -

not specified

Benign:1

Sep 30, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CHARGE syndrome

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CHARGE syndrome;C0342384:Hypogonadotropic hypogonadism 7 with or without anosmia

Benign:1

Apr 20, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.10

T;T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.61

.;T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.6

L;L;.

PhyloP100

0.40

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.50

N;.;N

REVEL

Benign

0.14

Sift

Benign

0.17

T;.;T

Sift4G

Benign

0.23

T;.;T

Polyphen

0.0

B;B;.

Vest4

0.091

MVP

0.81

MPC

0.20

ClinPred

0.0065

GERP RS

2.6

Varity_R

0.062

gMVP

0.51

Mutation Taster

=99/1

polymorphism

(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

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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