rs2272222

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006080.3(SEMA3A):c.668-14T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,579,162 control chromosomes in the GnomAD database, including 97,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16108 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81760 hom. )

Consequence

SEMA3A
NM_006080.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.307

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 7-84014365-A-T is Benign according to our data. Variant chr7-84014365-A-T is described in ClinVar as Benign. ClinVar VariationId is 1174649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3 link	c.668-14T>A	intron_variant	Intron 6 of 16	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 link	c.668-14T>A	intron_variant	Intron 9 of 19		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.668-14T>A	intron_variant	Intron 10 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9 link	c.668-14T>A		intron_variant	Intron 6 of 16	1	NM_006080.3	ENSP00000265362.3		Q14563
SEMA3A	ENST00000436949.5 link	c.668-14T>A		intron_variant	Intron 7 of 17	5		ENSP00000415260.1		Q14563

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65304

AN:

151510

Hom.:

16082

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.394

GnomAD2 exomes

AF:

0.365

AC:

90255

AN:

246946

AF XY:

0.364

show subpopulations

Gnomad AFR exome

AF:

0.696

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.343

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.329

AC:

469742

AN:

1427534

Hom.:

81760

Cov.:

AF XY:

0.332

AC XY:

236279

AN XY:

712100

show subpopulations

African (AFR)

AF:

0.701

AC:

22544

AN:

32168

American (AMR)

AF:

0.338

AC:

15006

AN:

44392

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

8641

AN:

25922

East Asian (EAS)

AF:

0.391

AC:

15396

AN:

39410

South Asian (SAS)

AF:

0.458

AC:

38984

AN:

85108

European-Finnish (FIN)

AF:

0.354

AC:

18076

AN:

51062

Middle Eastern (MID)

AF:

0.398

AC:

2265

AN:

5696

European-Non Finnish (NFE)

AF:

0.302

AC:

328055

AN:

1084504

Other (OTH)

AF:

0.351

AC:

20775

AN:

59272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

12911

25822

38734

51645

64556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10800

21600

32400

43200

54000

<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:

0.431

AC:

65382

AN:

151628

Hom.:

16108

Cov.:

AF XY:

0.432

AC XY:

32025

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.691

AC:

28513

AN:

41242

American (AMR)

AF:

0.361

AC:

5511

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1199

AN:

3468

East Asian (EAS)

AF:

0.363

AC:

1870

AN:

5148

South Asian (SAS)

AF:

0.453

AC:

2182

AN:

4812

European-Finnish (FIN)

AF:

0.342

AC:

3593

AN:

10502

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21313

AN:

67896

Other (OTH)

AF:

0.394

AC:

830

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1704

3408

5111

6815

8519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.370

Hom.:

2111

Bravo

AF:

0.443

Asia WGS

AF:

0.440

AC:

1531

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.3

(source)

DANN

Benign

0.83

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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