rs74349534

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006080.3(SEMA3A):c.267A>G(p.Gln89Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,608,202 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 123 hom. )

Consequence

SEMA3A
NM_006080.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.78

Publications

6 publications found

Variant links:

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

SEMA3A Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hypogonadotropic hypogonadism 16 with or without anosmia
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
Brugada syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SEMA3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 7-84134797-T-C is Benign according to our data. Variant chr7-84134797-T-C is described in ClinVar as Benign. ClinVar VariationId is 1293022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.78 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3 link	c.267A>G	p.Gln89Gln	synonymous_variant	Exon 2 of 17	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 link	c.267A>G	p.Gln89Gln	synonymous_variant	Exon 5 of 20		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.267A>G	p.Gln89Gln	synonymous_variant	Exon 6 of 21		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEMA3A	ENST00000265362.9 link	c.267A>G	p.Gln89Gln	synonymous_variant	Exon 2 of 17	1	NM_006080.3	ENSP00000265362.3	Q14563
SEMA3A	ENST00000436949.5 link	c.267A>G	p.Gln89Gln	synonymous_variant	Exon 3 of 18	5		ENSP00000415260.1	Q14563
SEMA3A	ENST00000420047.1 link	c.267A>G	p.Gln89Gln	synonymous_variant	Exon 3 of 5	4		ENSP00000391900.1	C9J9C4

Frequencies

GnomAD3 genomes

AF:

0.00873

AC:

1329

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00974

AC:

2407

AN:

247008

AF XY:

0.00976

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.00447

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0109

AC:

15861

AN:

1455848

Hom.:

123

Cov.:

AF XY:

0.0105

AC XY:

7579

AN XY:

724368

show subpopulations

African (AFR)

AF:

0.00138

AC:

AN:

33216

American (AMR)

AF:

0.00484

AC:

213

AN:

44002

Ashkenazi Jewish (ASJ)

AF:

0.00108

AC:

AN:

25952

East Asian (EAS)

AF:

0.00

AC:

AN:

39500

South Asian (SAS)

AF:

0.00131

AC:

112

AN:

85516

European-Finnish (FIN)

AF:

0.0297

AC:

1582

AN:

53304

Middle Eastern (MID)

AF:

0.00505

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0120

AC:

13338

AN:

1108486

Other (OTH)

AF:

0.00853

AC:

513

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

696

1393

2089

2786

3482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.00872

AC:

1329

AN:

152354

Hom.:

Cov.:

AF XY:

0.00934

AC XY:

696

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

41590

American (AMR)

AF:

0.00523

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0267

AC:

284

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0127

AC:

861

AN:

68042

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

142

213

284

355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0102

Hom.:

Bravo

AF:

0.00697

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SEMA3A: BP4, BP7, BS1, BS2 -

Mar 31, 2020

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

- -

SEMA3A-related disorder

Benign:1

Jun 15, 2021

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.9

(source)

DANN

Benign

0.57

PhyloP100

1.8

Mutation Taster

=100/0

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

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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