NM_020911.2:c.5611G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020911.2(PLXNA4):​c.5611G>A​(p.Asp1871Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PLXNA4
NM_020911.2 missense

Scores

2
9
8

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.13
Variant links:
Genes affected
PLXNA4 (HGNC:9102): (plexin A4) Predicted to enable semaphorin receptor activity. Predicted to be involved in several processes, including axon guidance; positive regulation of axonogenesis; and regulation of GTPase activity. Predicted to act upstream of or within several processes, including nervous system development; regulation of axon extension involved in axon guidance; and regulation of negative chemotaxis. Predicted to be located in plasma membrane. Predicted to be part of semaphorin receptor complex. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLXNA4NM_020911.2 linkc.5611G>A p.Asp1871Asn missense_variant Exon 32 of 32 ENST00000321063.9 NP_065962.1 Q9HCM2-1A0A024R7A6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLXNA4ENST00000321063.9 linkc.5611G>A p.Asp1871Asn missense_variant Exon 32 of 32 5 NM_020911.2 ENSP00000323194.4 Q9HCM2-1
PLXNA4ENST00000359827.7 linkc.5611G>A p.Asp1871Asn missense_variant Exon 32 of 32 5 ENSP00000352882.3 Q9HCM2-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152138
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000120
AC:
30
AN:
249320
Hom.:
0
AF XY:
0.000148
AC XY:
20
AN XY:
135270
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000230
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000132
AC:
193
AN:
1461830
Hom.:
0
Cov.:
61
AF XY:
0.000142
AC XY:
103
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000157
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152256
Hom.:
0
Cov.:
33
AF XY:
0.0000806
AC XY:
6
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000241
Hom.:
0
Bravo
AF:
0.000147
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.000157
AC:
19
EpiCase
AF:
0.000164
EpiControl
AF:
0.000356

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

PLXNA4-related disorder Uncertain:1
Dec 29, 2023
PreventionGenetics, part of Exact Sciences
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

The PLXNA4 c.5611G>A variant is predicted to result in the amino acid substitution p.Asp1871Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of European (Non-Finnish) 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
Benign
0.11
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.56
D;D
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;.
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.70
D;D
MetaSVM
Benign
-0.81
T
MutationAssessor
Uncertain
2.9
M;M
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-4.4
D;D
REVEL
Benign
0.29
Sift
Uncertain
0.0010
D;D
Sift4G
Benign
0.10
T;T
Polyphen
1.0
D;D
Vest4
0.56
MVP
0.52
MPC
1.4
ClinPred
0.93
D
GERP RS
5.5
Varity_R
0.61
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs201799383; hg19: chr7-131815312; API