3-126988679-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032242.4(PLXNA1):​c.86G>A​(p.Gly29Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,426,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G29A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PLXNA1
NM_032242.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.02

Publications

0 publications found
Variant links:
Genes affected
PLXNA1 (HGNC:9099): (plexin A1) Predicted to enable semaphorin receptor activity. Predicted to be involved in several processes, including generation of neurons; regulation of GTPase activity; and regulation of cell shape. Predicted to act upstream of or within dichotomous subdivision of terminal units involved in salivary gland branching; neuron projection morphogenesis; and regulation of smooth muscle cell migration. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
PLXNA1 Gene-Disease associations (from GenCC):
  • Dworschak-Punetha neurodevelopmental syndrome
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: LIMITED Submitted by: G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23380676).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLXNA1NM_032242.4 linkc.86G>A p.Gly29Asp missense_variant Exon 2 of 32 ENST00000393409.3 NP_115618.3 Q9UIW2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLXNA1ENST00000393409.3 linkc.86G>A p.Gly29Asp missense_variant Exon 2 of 32 1 NM_032242.4 ENSP00000377061.2 Q9UIW2
PLXNA1ENST00000684469.1 linkc.86G>A p.Gly29Asp missense_variant Exon 2 of 2 ENSP00000507976.1 A0A804HKL4

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
217980
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
7.01e-7
AC:
1
AN:
1426120
Hom.:
0
Cov.:
33
AF XY:
0.00000142
AC XY:
1
AN XY:
705052
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32858
American (AMR)
AF:
0.00
AC:
0
AN:
42014
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23784
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39338
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79856
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50782
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5594
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1093042
Other (OTH)
AF:
0.0000170
AC:
1
AN:
58852
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
14
DANN
Benign
0.84
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.76
D
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.0
N
PhyloP100
4.0
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.046
Sift
Benign
0.18
T
Sift4G
Benign
0.63
T
Polyphen
0.0030
B
Vest4
0.50
MutPred
0.42
Gain of relative solvent accessibility (P = 0.0082);
MVP
0.32
MPC
0.58
ClinPred
0.051
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.049
gMVP
0.62
Mutation Taster
=85/15
polymorphism

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

Other links and lift over

dbSNP: rs779320185; hg19: chr3-126707522; API