NM_012431.3:c.603G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012431.3(SEMA3E):c.603G>T(p.Ala201Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,613,168 control chromosomes in the GnomAD database, including 294,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22454 hom., cov: 33)

Exomes 𝑓: 0.60 ( 271969 hom. )

Consequence

SEMA3E
NM_012431.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.85

Publications

28 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 7-83408435-C-A is Benign according to our data. Variant chr7-83408435-C-A is described in ClinVar as Benign. ClinVar VariationId is 260255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3 link	c.603G>T	p.Ala201Ala	synonymous_variant	Exon 6 of 17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2 link	c.423G>T	p.Ala141Ala	synonymous_variant	Exon 6 of 17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2 link	c.603G>T	p.Ala201Ala	synonymous_variant	Exon 6 of 17		NM_012431.3	ENSP00000496491.1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77125

AN:

151964

Hom.:

22439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.530

GnomAD2 exomes

AF:

0.616

AC:

154315

AN:

250570

AF XY:

0.617

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.707

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.879

Gnomad FIN exome

AF:

0.669

Gnomad NFE exome

AF:

0.600

Gnomad OTH exome

AF:

0.601

GnomAD4 exome

AF:

0.604

AC:

882062

AN:

1461086

Hom.:

271969

Cov.:

AF XY:

0.604

AC XY:

439322

AN XY:

726802

show subpopulations

African (AFR)

AF:

0.190

AC:

6350

AN:

33460

American (AMR)

AF:

0.700

AC:

31234

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

11523

AN:

26130

East Asian (EAS)

AF:

0.833

AC:

33041

AN:

39678

South Asian (SAS)

AF:

0.653

AC:

56300

AN:

86242

European-Finnish (FIN)

AF:

0.668

AC:

35629

AN:

53370

Middle Eastern (MID)

AF:

0.484

AC:

2788

AN:

5764

European-Non Finnish (NFE)

AF:

0.603

AC:

670076

AN:

1111480

Other (OTH)

AF:

0.582

AC:

35121

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

18463

36926

55388

73851

92314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18176

36352

54528

72704

90880

<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:

0.507

AC:

77153

AN:

152082

Hom.:

22454

Cov.:

AF XY:

0.517

AC XY:

38452

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.209

AC:

8661

AN:

41506

American (AMR)

AF:

0.628

AC:

9573

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1541

AN:

3468

East Asian (EAS)

AF:

0.849

AC:

4385

AN:

5166

South Asian (SAS)

AF:

0.675

AC:

3258

AN:

4824

European-Finnish (FIN)

AF:

0.678

AC:

7166

AN:

10574

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.598

AC:

40681

AN:

67980

Other (OTH)

AF:

0.532

AC:

1121

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1676

3352

5028

6704

8380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.559

Hom.:

67726

Bravo

AF:

0.493

Asia WGS

AF:

0.741

AC:

2577

AN:

3478

EpiCase

AF:

0.587

EpiControl

AF:

0.582

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CHARGE syndrome

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.70

(source)

DANN

Benign

0.62

PhyloP100

-4.8

Mutation Taster

=85/15

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

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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