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GeneBe

X-154460393-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_017514.5(PLXNA3):c.210C>T(p.Pro70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,206,074 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 0 hem., cov: 25)
Exomes 𝑓: 0.000097 ( 0 hom. 22 hem. )

Consequence

PLXNA3
NM_017514.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.02
Variant links:
Genes affected
PLXNA3 (HGNC:9101): (plexin A3) This gene encodes a member of the plexin class of proteins. The encoded protein is a class 3 semaphorin receptor, and may be involved in cytoskeletal remodeling and as well as apoptosis. Studies of a similar gene in zebrafish suggest that it is important for axon pathfinding in the developing nervous system. This gene may be associated with tumor progression. [provided by RefSeq, Aug 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-154460393-C-T is Benign according to our data. Variant chrX-154460393-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048627.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154460393-C-T is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-6.02 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAdExome at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLXNA3NM_017514.5 linkuse as main transcriptc.210C>T p.Pro70= synonymous_variant 2/33 ENST00000369682.4
PLXNA3XM_047442247.1 linkuse as main transcriptc.210C>T p.Pro70= synonymous_variant 2/22
PLXNA3XR_007068193.1 linkuse as main transcriptn.385C>T non_coding_transcript_exon_variant 2/32
PLXNA3XR_430556.4 linkuse as main transcriptn.385C>T non_coding_transcript_exon_variant 2/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLXNA3ENST00000369682.4 linkuse as main transcriptc.210C>T p.Pro70= synonymous_variant 2/331 NM_017514.5 P1
PLXNA3ENST00000495040.1 linkuse as main transcriptn.146-706C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000798
AC:
9
AN:
112832
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
34984
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000278
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:
0.000113
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000809
AC:
14
AN:
173058
Hom.:
0
AF XY:
0.0000824
AC XY:
5
AN XY:
60674
show subpopulations
Gnomad AFR exome
AF:
0.0000797
Gnomad AMR exome
AF:
0.0000746
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000516
Gnomad SAS exome
AF:
0.000111
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000970
AC:
106
AN:
1093186
Hom.:
0
Cov.:
31
AF XY:
0.0000612
AC XY:
22
AN XY:
359430
show subpopulations
Gnomad4 AFR exome
AF:
0.0000759
Gnomad4 AMR exome
AF:
0.0000859
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000365
Gnomad4 SAS exome
AF:
0.0000933
Gnomad4 FIN exome
AF:
0.0000757
Gnomad4 NFE exome
AF:
0.0000905
Gnomad4 OTH exome
AF:
0.000131
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000797
AC:
9
AN:
112888
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
35050
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000278
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000113
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000982

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PLXNA3-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 27, 2019This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
0.076
Dann
Benign
0.79

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: rs57535644; hg19: chrX-153688733; API