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GeneBe

7-83961420-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006080.3(SEMA3A):c.2267G>A(p.Gly756Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SEMA3A
NM_006080.3 missense

Scores

3
5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38378567).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA3ANM_006080.3 linkuse as main transcriptc.2267G>A p.Gly756Asp missense_variant 17/17 ENST00000265362.9
SEMA3AXM_005250110.4 linkuse as main transcriptc.2267G>A p.Gly756Asp missense_variant 20/20
SEMA3AXM_047419751.1 linkuse as main transcriptc.2267G>A p.Gly756Asp missense_variant 21/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA3AENST00000265362.9 linkuse as main transcriptc.2267G>A p.Gly756Asp missense_variant 17/171 NM_006080.3 P1
SEMA3AENST00000436949.5 linkuse as main transcriptc.2267G>A p.Gly756Asp missense_variant 18/185 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251444
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
6.84e-7
AC:
1
AN:
1461802
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SEMA3A-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 18, 2023The SEMA3A c.2267G>A variant is predicted to result in the amino acid substitution p.Gly756Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. 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
Pathogenic
0.85
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.23
Cadd
Uncertain
25
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.48
T;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.17
Sift
Benign
0.41
T;T
Sift4G
Benign
0.63
T;T
Polyphen
0.97
D;D
Vest4
0.48
MutPred
0.34
Gain of glycosylation at K754 (P = 0.1146);Gain of glycosylation at K754 (P = 0.1146);
MVP
0.53
MPC
0.98
ClinPred
0.88
D
GERP RS
4.2
Varity_R
0.15
gMVP
0.50

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.

Other links and lift over

dbSNP: rs754608912; hg19: chr7-83590736; COSMIC: COSV54862441; API