rs7804122

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.1302T>C(p.Ile434Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,612,230 control chromosomes in the GnomAD database, including 44,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4649 hom., cov: 31)

Exomes 𝑓: 0.23 ( 39768 hom. )

Consequence

SEMA3A
NM_006080.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.274

Publications

24 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=-0.56).

BP6

Variant 7-84005397-A-G is Benign according to our data. Variant chr7-84005397-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.274 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3 link	c.1302T>C	p.Ile434Ile	synonymous_variant	Exon 11 of 17	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 link	c.1302T>C	p.Ile434Ile	synonymous_variant	Exon 14 of 20		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.1302T>C	p.Ile434Ile	synonymous_variant	Exon 15 of 21		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9 link	c.1302T>C	p.Ile434Ile	synonymous_variant	Exon 11 of 17	1	NM_006080.3	ENSP00000265362.3		Q14563
SEMA3A	ENST00000436949.5 link	c.1302T>C	p.Ile434Ile	synonymous_variant	Exon 12 of 18	5		ENSP00000415260.1		Q14563

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36905

AN:

151844

Hom.:

4646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.238

AC:

59845

AN:

251304

AF XY:

0.246

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.230

AC:

336028

AN:

1460268

Hom.:

39768

Cov.:

AF XY:

0.233

AC XY:

169381

AN XY:

726532

show subpopulations

African (AFR)

AF:

0.265

AC:

8856

AN:

33460

American (AMR)

AF:

0.175

AC:

7847

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

6376

AN:

26112

East Asian (EAS)

AF:

0.166

AC:

6605

AN:

39674

South Asian (SAS)

AF:

0.319

AC:

27466

AN:

86214

European-Finnish (FIN)

AF:

0.303

AC:

16161

AN:

53374

Middle Eastern (MID)

AF:

0.331

AC:

1907

AN:

5758

European-Non Finnish (NFE)

AF:

0.222

AC:

246524

AN:

1110622

Other (OTH)

AF:

0.237

AC:

14286

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

12286

24572

36859

49145

61431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8438

16876

25314

33752

42190

<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:

0.243

AC:

36921

AN:

151962

Hom.:

4649

Cov.:

AF XY:

0.247

AC XY:

18329

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.268

AC:

11086

AN:

41430

American (AMR)

AF:

0.204

AC:

3124

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

867

AN:

3466

East Asian (EAS)

AF:

0.163

AC:

840

AN:

5162

South Asian (SAS)

AF:

0.314

AC:

1512

AN:

4814

European-Finnish (FIN)

AF:

0.301

AC:

3177

AN:

10540

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.228

AC:

15508

AN:

67954

Other (OTH)

AF:

0.235

AC:

494

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1377

2754

4131

5508

6885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.221

Hom.:

12298

Bravo

AF:

0.235

Asia WGS

AF:

0.235

AC:

820

AN:

3478

EpiCase

AF:

0.250

EpiControl

AF:

0.243

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Aug 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.4

(source)

DANN

Benign

0.72

PhyloP100

-0.27

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

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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