rs142204796

Positions:

chr7-83367812-C-A

Variant summary

Our verdict is Benign. Variant got -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 218701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83367812-C-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 628 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3E	NM_012431.3 linkuse as main transcript	c.2102G>T	p.Ser701Ile	missense_variant	17/17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2 linkuse as main transcript	c.1922G>T	p.Ser641Ile	missense_variant	17/17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2 linkuse as main transcript	c.2102G>T	p.Ser701Ile	missense_variant	17/17		NM_012431.3	ENSP00000496491	P1	O15041-1
SEMA3E	ENST00000643441.1 linkuse as main transcript	n.2087G>T		non_coding_transcript_exon_variant	17/17

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

GnomAD3 exomes

AF:

0.00537

AC:

1350

AN:

251402

Hom.:

AF XY:

0.00561

AC XY:

762

AN XY:

135878

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 SAS exome

AF:

0.0111

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

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.0161

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.00163

Gnomad4 NFE exome

AF:

0.00564

Gnomad4 OTH exome

AF:

0.00669

GnomAD4 genome

AF:

0.00412

AC:

628

AN:

152246

Hom.:

Cov.:

AF XY:

0.00412

AC XY:

307

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00515

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00544

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 31, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	SEMA3E: BP4, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Sep 30, 2015

- -

CHARGE syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 20, 2022

- -

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

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;.

MutationTaster

Benign

1.0

N;N

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over