NM_006080.3:c.1563G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006080.3(SEMA3A):c.1563G>C(p.Gly521Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,613,724 control chromosomes in the GnomAD database, including 2,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G521G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.026 ( 165 hom., cov: 32)

Exomes 𝑓: 0.030 ( 2158 hom. )

Consequence

SEMA3A
NM_006080.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.202

Publications

14 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, SD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 7-83981410-C-G is Benign according to our data. Variant chr7-83981410-C-G is described in ClinVar as Benign. ClinVar VariationId is 1262671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.202 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	NM_006080.3	MANE Select	c.1563G>C	p.Gly521Gly	synonymous	Exon 14 of 17	NP_006071.1	Q14563

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA3A	ENST00000265362.9	TSL:1 MANE Select	c.1563G>C	p.Gly521Gly	synonymous	Exon 14 of 17	ENSP00000265362.3	Q14563
SEMA3A	ENST00000436949.5	TSL:5	c.1563G>C	p.Gly521Gly	synonymous	Exon 15 of 18	ENSP00000415260.1	Q14563
SEMA3A	ENST00000864988.1		c.1563G>C	p.Gly521Gly	synonymous	Exon 19 of 22	ENSP00000535047.1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3932

AN:

152086

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0426

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.0505

AC:

12670

AN:

250762

AF XY:

0.0500

show subpopulations

Gnomad AFR exome

AF:

0.00881

Gnomad AMR exome

AF:

0.0976

Gnomad ASJ exome

AF:

0.0322

Gnomad EAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.00301

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0390

GnomAD4 exome

AF:

0.0300

AC:

43847

AN:

1461520

Hom.:

2158

Cov.:

AF XY:

0.0318

AC XY:

23122

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.00947

AC:

317

AN:

33466

American (AMR)

AF:

0.0925

AC:

4134

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.0299

AC:

780

AN:

26130

East Asian (EAS)

AF:

0.229

AC:

9070

AN:

39672

South Asian (SAS)

AF:

0.106

AC:

9110

AN:

86220

European-Finnish (FIN)

AF:

0.00348

AC:

186

AN:

53392

Middle Eastern (MID)

AF:

0.0239

AC:

138

AN:

5766

European-Non Finnish (NFE)

AF:

0.0162

AC:

17974

AN:

1111814

Other (OTH)

AF:

0.0354

AC:

2138

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1949

3898

5848

7797

9746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

920

1840

2760

3680

4600

<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:

0.0259

AC:

3935

AN:

152204

Hom.:

165

Cov.:

AF XY:

0.0284

AC XY:

2115

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0110

AC:

455

AN:

41534

American (AMR)

AF:

0.0427

AC:

653

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3470

East Asian (EAS)

AF:

0.194

AC:

1002

AN:

5158

South Asian (SAS)

AF:

0.117

AC:

563

AN:

4818

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0155

AC:

1054

AN:

68000

Other (OTH)

AF:

0.0303

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

170

340

511

681

851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0191

Hom.:

Bravo

AF:

0.0274

Asia WGS

AF:

0.160

AC:

559

AN:

3478

EpiCase

AF:

0.0167

EpiControl

AF:

0.0178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.8

(source)

DANN

Benign

0.65

PhyloP100

-0.20

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over