rs144370841

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_012431.3(SEMA3E):c.2048A>G(p.Asn683Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,612,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SEMA3E
NM_012431.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -0.0750

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0083453655).

BP6

Variant 7-83367866-T-C is Benign according to our data. Variant chr7-83367866-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 459536.

BS2

High AC in GnomAd4 at 43 AD,Unknown gene.

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.2048A>G	p.Asn683Ser	missense	Exon 17 of 17	NP_036563.1	O15041-1
	SEMA3E	NM_001178129.2		c.1868A>G	p.Asn623Ser	missense	Exon 17 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.2048A>G	p.Asn683Ser	missense	Exon 17 of 17	ENSP00000496491.1	O15041-1
SEMA3E	ENST00000891111.1		c.2042A>G	p.Asn681Ser	missense	Exon 17 of 17	ENSP00000561170.1
SEMA3E	ENST00000643441.1		n.2033A>G		non_coding_transcript_exon	Exon 17 of 17

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.0000758

AC:

AN:

250536

AF XY:

0.0000517

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1460144

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726080

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

33384

American (AMR)

AF:

0.0000224

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26032

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110774

Other (OTH)

AF:

0.0000498

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000282

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.000963

AC:

AN:

41544

American (AMR)

AF:

0.0000654

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000299

Hom.:

Bravo

AF:

0.000400

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

CHARGE syndrome (1)

not provided (1)

not specified (1)

SEMA3E-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.68

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.042

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.70

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.32

PhyloP100

-0.075

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.40

REVEL

Benign

0.022

Sift

Benign

0.79

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.043

MVP

0.34

MPC

0.13

ClinPred

0.0062

GERP RS

0.87

Varity_R

0.027

gMVP

0.15

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

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