Variant rs74349534 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006080.3(SEMA3A):c.267A>G(p.Gln89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,608,202 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 123 hom. )

Consequence

SEMA3A
NM_006080.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.78

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 7-84134797-T-C is Benign according to our data. Variant chr7-84134797-T-C is described in ClinVar as [Benign]. Clinvar id is 1293022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.78 with no splicing effect.

BS2

High AC in GnomAd4 at 1329 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SEMA3A	NM_006080.3 linkuse as main transcript	c.267A>G	p.Gln89=	synonymous_variant	2/17	ENST00000265362.9
SEMA3A	XM_005250110.4 linkuse as main transcript	c.267A>G	p.Gln89=	synonymous_variant	5/20
SEMA3A	XM_047419751.1 linkuse as main transcript	c.267A>G	p.Gln89=	synonymous_variant	6/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SEMA3A	ENST00000265362.9 linkuse as main transcript	c.267A>G	p.Gln89=	synonymous_variant	2/17	1	NM_006080.3	P1
SEMA3A	ENST00000436949.5 linkuse as main transcript	c.267A>G	p.Gln89=	synonymous_variant	3/18	5		P1
SEMA3A	ENST00000420047.1 linkuse as main transcript	c.267A>G	p.Gln89=	synonymous_variant	3/5	4

Frequencies

GnomAD3 genomes

AF:

0.00873

AC:

1329

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00974

AC:

2407

AN:

247008

Hom.:

AF XY:

0.00976

AC XY:

1303

AN XY:

133564

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.00447

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0109

AC:

15861

AN:

1455848

Hom.:

123

Cov.:

AF XY:

0.0105

AC XY:

7579

AN XY:

724368

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00484

Gnomad4 ASJ exome

AF:

0.00108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.0297

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.00853

GnomAD4 genome

AF:

0.00872

AC:

1329

AN:

152354

Hom.:

Cov.:

AF XY:

0.00934

AC XY:

696

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.0267

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00697

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	SEMA3A: BP4, BP7, BS1, BS2 -

SEMA3A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 15, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.9

DANN

Benign

0.57

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