7-83961733-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006080.3(SEMA3A):c.1954G>A(p.Val652Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000979 in 1,613,878 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 3 hom. )
Consequence
SEMA3A
NM_006080.3 missense
NM_006080.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.01
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0872508).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA3A | NM_006080.3 | c.1954G>A | p.Val652Met | missense_variant | 17/17 | ENST00000265362.9 | |
SEMA3A | XM_005250110.4 | c.1954G>A | p.Val652Met | missense_variant | 20/20 | ||
SEMA3A | XM_047419751.1 | c.1954G>A | p.Val652Met | missense_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA3A | ENST00000265362.9 | c.1954G>A | p.Val652Met | missense_variant | 17/17 | 1 | NM_006080.3 | P1 | |
SEMA3A | ENST00000436949.5 | c.1954G>A | p.Val652Met | missense_variant | 18/18 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152128Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
5
AN:
152128
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000195 AC: 49AN: 251076Hom.: 0 AF XY: 0.000251 AC XY: 34AN XY: 135698
GnomAD3 exomes
AF:
AC:
49
AN:
251076
Hom.:
AF XY:
AC XY:
34
AN XY:
135698
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000105 AC: 153AN: 1461632Hom.: 3 Cov.: 33 AF XY: 0.000149 AC XY: 108AN XY: 727126
GnomAD4 exome
AF:
AC:
153
AN:
1461632
Hom.:
Cov.:
33
AF XY:
AC XY:
108
AN XY:
727126
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74416
GnomAD4 genome
AF:
AC:
5
AN:
152246
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74416
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
24
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2023 | The c.1954G>A (p.V652M) alteration is located in exon 17 (coding exon 17) of the SEMA3A gene. This alteration results from a G to A substitution at nucleotide position 1954, causing the valine (V) at amino acid position 652 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
SEMA3A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 05, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Gain of catalytic residue at V652 (P = 0.1726);Gain of catalytic residue at V652 (P = 0.1726);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at