rs797821

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006080.3(SEMA3A):c.2151A>G(p.Thr717Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,613,714 control chromosomes in the GnomAD database, including 311,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26405 hom., cov: 32)

Exomes 𝑓: 0.62 ( 284689 hom. )

Consequence

SEMA3A
NM_006080.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.09

Publications

28 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-83961536-T-C is Benign according to our data. Variant chr7-83961536-T-C is described in ClinVar as Benign. ClinVar VariationId is 194754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3 link	c.2151A>G	p.Thr717Thr	synonymous_variant	Exon 17 of 17	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 link	c.2151A>G	p.Thr717Thr	synonymous_variant	Exon 20 of 20		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.2151A>G	p.Thr717Thr	synonymous_variant	Exon 21 of 21		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9 link	c.2151A>G	p.Thr717Thr	synonymous_variant	Exon 17 of 17	1	NM_006080.3	ENSP00000265362.3		Q14563
SEMA3A	ENST00000436949.5 link	c.2151A>G	p.Thr717Thr	synonymous_variant	Exon 18 of 18	5		ENSP00000415260.1		Q14563

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88891

AN:

151880

Hom.:

26389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.692

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.626

GnomAD2 exomes

AF:

0.616

AC:

154900

AN:

251352

AF XY:

0.616

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.656

Gnomad ASJ exome

AF:

0.632

Gnomad EAS exome

AF:

0.707

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.626

Gnomad OTH exome

AF:

0.619

GnomAD4 exome

AF:

0.623

AC:

910368

AN:

1461718

Hom.:

284689

Cov.:

AF XY:

0.623

AC XY:

452812

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.491

AC:

16436

AN:

33470

American (AMR)

AF:

0.656

AC:

29360

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

16427

AN:

26136

East Asian (EAS)

AF:

0.668

AC:

26513

AN:

39700

South Asian (SAS)

AF:

0.592

AC:

51096

AN:

86254

European-Finnish (FIN)

AF:

0.549

AC:

29304

AN:

53418

Middle Eastern (MID)

AF:

0.576

AC:

3320

AN:

5768

European-Non Finnish (NFE)

AF:

0.630

AC:

700753

AN:

1111864

Other (OTH)

AF:

0.615

AC:

37159

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

20510

41020

61529

82039

102549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18690

37380

56070

74760

93450

<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:

0.585

AC:

88939

AN:

151996

Hom.:

26405

Cov.:

AF XY:

0.581

AC XY:

43134

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.490

AC:

20298

AN:

41440

American (AMR)

AF:

0.624

AC:

9530

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

2229

AN:

3472

East Asian (EAS)

AF:

0.692

AC:

3568

AN:

5156

South Asian (SAS)

AF:

0.597

AC:

2879

AN:

4820

European-Finnish (FIN)

AF:

0.550

AC:

5809

AN:

10556

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.627

AC:

42618

AN:

67968

Other (OTH)

AF:

0.629

AC:

1322

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1891

3783

5674

7566

9457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.617

Hom.:

58054

Bravo

AF:

0.589

Asia WGS

AF:

0.634

AC:

2203

AN:

3478

EpiCase

AF:

0.619

EpiControl

AF:

0.625

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 11, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Aug 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.026

(source)

DANN

Benign

0.48

PhyloP100

-1.1

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over