X-154460321-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_017514.5(PLXNA3):c.138C>T(p.Phe46=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000321 in 1,209,056 control chromosomes in the GnomAD database, including 2 homozygotes. There are 119 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 0.00028 (0 hom., 7 hem., cov: 25)
  • Exomes 𝑓: 0.00033 (2 hom. 112 hem.)
• Consequence: PLXNA3 NM_017514.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-154460321-C-T is Benign according to our data. Variant chrX-154460321-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 749131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-154460321-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.36 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA3	NM_017514.5	c.138C>T	p.Phe46=	synonymous_variant	2/33	ENST00000369682.4
PLXNA3	XM_047442247.1	c.138C>T	p.Phe46=	synonymous_variant	2/22
PLXNA3	XR_007068193.1	n.313C>T		non_coding_transcript_exon_variant	2/32
PLXNA3	XR_430556.4	n.313C>T		non_coding_transcript_exon_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA3	ENST00000369682.4	c.138C>T	p.Phe46=	synonymous_variant	2/33	1	NM_017514.5	P1
PLXNA3	ENST00000495040.1	n.146-778C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 31 AN: 112122 Hom.: 0 Cov.: 25 AF XY: 0.000204 AC XY: 7 AN XY: 34310

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000374

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000841

Gnomad SAS AF: 0.000731

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000377

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000366 AC: 66 AN: 180450 Hom.: 0 AF XY: 0.000272 AC XY: 18 AN XY: 66080

Gnomad AFR exome AF: 0.0000768

Gnomad AMR exome AF: 0.000476

Gnomad ASJ exome AF: 0.000135

Gnomad EAS exome AF: 0.000145

Gnomad SAS exome AF: 0.000578

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000465

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.000325 AC: 357 AN: 1096881 Hom.: 2 Cov.: 31 AF XY: 0.000309 AC XY: 112 AN XY: 362643

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.000398

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000662

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000343

Gnomad4 OTH exome AF: 0.000326

GnomAD4 genome AF: 0.000276 AC: 31 AN: 112175 Hom.: 0 Cov.: 25 AF XY: 0.000204 AC XY: 7 AN XY: 34373

Gnomad4 AFR AF: 0.0000324

Gnomad4 AMR AF: 0.000374

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000843

Gnomad4 SAS AF: 0.000733

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000377

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000291 Hom.: 3

Bravo AF: 0.000200

EpiCase AF: 0.000818

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PLXNA3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 08, 2023

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). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	1.0
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs147816954; hg19: chrX-153688661;