7-83400122-C-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.1272G>A(p.Leu424Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,613,362 control chromosomes in the GnomAD database, including 159,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11704 hom., cov: 31)

Exomes 𝑓: 0.45 ( 148046 hom. )

Consequence

SEMA3E
NM_012431.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.06

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 7-83400122-C-T is Benign according to our data. Variant chr7-83400122-C-T is described in ClinVar as Benign. ClinVar VariationId is 260254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012431.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	NM_012431.3	MANE Select	c.1272G>A	p.Leu424Leu	synonymous	Exon 11 of 17	NP_036563.1
	SEMA3E	NM_001178129.2		c.1092G>A	p.Leu364Leu	synonymous	Exon 11 of 17	NP_001171600.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SEMA3E	ENST00000643230.2	MANE Select	c.1272G>A	p.Leu424Leu	synonymous	Exon 11 of 17	ENSP00000496491.1
SEMA3E	ENST00000642232.1		c.1272G>A	p.Leu424Leu	synonymous	Exon 11 of 17	ENSP00000494064.1
SEMA3E	ENST00000643441.1		n.1257G>A		non_coding_transcript_exon	Exon 11 of 17

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54754

AN:

151726

Hom.:

11688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.374

GnomAD2 exomes

AF:

0.425

AC:

106757

AN:

251224

AF XY:

0.430

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.454

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.446

AC:

651188

AN:

1461518

Hom.:

148046

Cov.:

AF XY:

0.446

AC XY:

323995

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.106

AC:

3541

AN:

33478

American (AMR)

AF:

0.421

AC:

18815

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

7888

AN:

26130

East Asian (EAS)

AF:

0.450

AC:

17870

AN:

39678

South Asian (SAS)

AF:

0.453

AC:

39034

AN:

86250

European-Finnish (FIN)

AF:

0.496

AC:

26499

AN:

53420

Middle Eastern (MID)

AF:

0.358

AC:

2066

AN:

5768

European-Non Finnish (NFE)

AF:

0.459

AC:

509919

AN:

1111692

Other (OTH)

AF:

0.423

AC:

25556

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20182

40365

60547

80730

100912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15144

30288

45432

60576

75720

<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:

0.361

AC:

54779

AN:

151844

Hom.:

11704

Cov.:

AF XY:

0.366

AC XY:

27174

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.119

AC:

4945

AN:

41412

American (AMR)

AF:

0.410

AC:

6252

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1067

AN:

3464

East Asian (EAS)

AF:

0.456

AC:

2340

AN:

5134

South Asian (SAS)

AF:

0.460

AC:

2208

AN:

4804

European-Finnish (FIN)

AF:

0.513

AC:

5399

AN:

10530

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

31129

AN:

67942

Other (OTH)

AF:

0.378

AC:

798

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1626

3253

4879

6506

8132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.399

Hom.:

7155

Bravo

AF:

0.340

Asia WGS

AF:

0.469

AC:

1630

AN:

3476

EpiCase

AF:

0.446

EpiControl

AF:

0.439

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 30, 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

CHARGE syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.3

(source)

DANN

Benign

0.64

PhyloP100

-1.1

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over