rs61636768

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1566T>C(p.Tyr522Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00709 in 1,613,842 control chromosomes in the GnomAD database, including 667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 320 hom., cov: 31)

Exomes 𝑓: 0.0041 ( 347 hom. )

Consequence

SEMA3E
NM_012431.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.666

Publications

1 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):

CHD7-related CHARGE syndrome
Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
CHARGE syndrome
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Kallmann syndrome
Inheritance: AD Classification: LIMITED Submitted by: 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=-0.57).

BP6

Variant 7-83392656-A-G is Benign according to our data. Variant chr7-83392656-A-G is described in ClinVar as Benign. ClinVar VariationId is 416919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.666 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	NM_012431.3	MANE Select	c.1566T>C	p.Tyr522Tyr	synonymous	Exon 14 of 17	NP_036563.1	O15041-1
	SEMA3E	NM_001178129.2		c.1386T>C	p.Tyr462Tyr	synonymous	Exon 14 of 17	NP_001171600.1	O15041-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA3E	ENST00000643230.2	MANE Select	c.1566T>C	p.Tyr522Tyr	synonymous	Exon 14 of 17	ENSP00000496491.1	O15041-1
SEMA3E	ENST00000891111.1		c.1560T>C	p.Tyr520Tyr	synonymous	Exon 14 of 17	ENSP00000561170.1
SEMA3E	ENST00000642232.1		c.1566T>C	p.Tyr522Tyr	synonymous	Exon 14 of 17	ENSP00000494064.1	A0A2R8YCX5

Frequencies

GnomAD3 genomes

AF:

0.0353

AC:

5363

AN:

152028

Hom.:

315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.00949

AC:

2382

AN:

250944

AF XY:

0.00700

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.00680

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000891

Gnomad OTH exome

AF:

0.00735

GnomAD4 exome

AF:

0.00415

AC:

6059

AN:

1461696

Hom.:

347

Cov.:

AF XY:

0.00368

AC XY:

2677

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.131

AC:

4372

AN:

33462

American (AMR)

AF:

0.00765

AC:

342

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.000919

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0203

AC:

117

AN:

5762

European-Non Finnish (NFE)

AF:

0.000545

AC:

606

AN:

1111880

Other (OTH)

AF:

0.00937

AC:

566

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

312

624

937

1249

1561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

296

444

592

740

<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:

0.0354

AC:

5388

AN:

152146

Hom.:

320

Cov.:

AF XY:

0.0339

AC XY:

2523

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.122

AC:

5074

AN:

41484

American (AMR)

AF:

0.0138

AC:

210

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68014

Other (OTH)

AF:

0.0203

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

242

484

725

967

1209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0139

Hom.:

Bravo

AF:

0.0408

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.00172

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

CHARGE syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.72

(source)

DANN

Benign

0.43

PhyloP100

-0.67

Mutation Taster

=93/7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over