Variant 7-83961590-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006080.3(SEMA3A):c.2097G>T(p.Gln699His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 1 hom. )

Consequence

SEMA3A
NM_006080.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.878

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057457656).

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SEMA3A	NM_006080.3 linkuse as main transcript	c.2097G>T	p.Gln699His	missense_variant	17/17	ENST00000265362.9
SEMA3A	XM_005250110.4 linkuse as main transcript	c.2097G>T	p.Gln699His	missense_variant	20/20
SEMA3A	XM_047419751.1 linkuse as main transcript	c.2097G>T	p.Gln699His	missense_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9 linkuse as main transcript	c.2097G>T	p.Gln699His	missense_variant	17/17	1	NM_006080.3	P1
SEMA3A	ENST00000436949.5 linkuse as main transcript	c.2097G>T	p.Gln699His	missense_variant	18/18	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000835

AC:

AN:

251376

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3A-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 25, 2024

The SEMA3A c.2097G>T variant is predicted to result in the amino acid substitution p.Gln699His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.061% of alleles in individuals of Latino descent in gnomAD, which may be too common to be an unreported primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.024

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.60

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.16

Sift

Benign

0.58

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0090

B;B

Vest4

0.26

MutPred

0.29

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.80

MPC

0.25

ClinPred

0.073

GERP RS

4.3

Varity_R

0.042

gMVP

0.51

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