Variant rs10487865 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1262671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83981410-C-G is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3A	NM_006080.3 linkuse as main transcript	c.1563G>C	p.Gly521Gly	synonymous_variant	14/17	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 linkuse as main transcript	c.1563G>C	p.Gly521Gly	synonymous_variant	17/20		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 linkuse as main transcript	c.1563G>C	p.Gly521Gly	synonymous_variant	18/21		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9 linkuse as main transcript	c.1563G>C	p.Gly521Gly	synonymous_variant	14/17	1	NM_006080.3	ENSP00000265362.3		Q14563
SEMA3A	ENST00000436949.5 linkuse as main transcript	c.1563G>C	p.Gly521Gly	synonymous_variant	15/18	5		ENSP00000415260.1		Q14563

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

GnomAD3 exomes

AF:

0.0505

AC:

12670

AN:

250762

Hom.:

750

AF XY:

0.0500

AC XY:

6773

AN XY:

135572

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 SAS exome

AF:

0.111

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

Gnomad4 AFR exome

AF:

0.00947

Gnomad4 AMR exome

AF:

0.0925

Gnomad4 ASJ exome

AF:

0.0299

Gnomad4 EAS exome

AF:

0.229

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.00348

Gnomad4 NFE exome

AF:

0.0162

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0259

AC:

3935

AN:

152204

Hom.:

165

Cov.:

AF XY:

0.0284

AC XY:

2115

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0427

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.0303

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.8

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over