Genetic Variant NM_017514.5:c.49dupG (chrX-154460224-T-TG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_StrongBS2

The NM_017514.5(PLXNA3):c.49dupG(p.Ala17GlyfsTer39) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,080,797 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.000062 ( 0 hom. 3 hem. )

Failed GnomAD Quality Control

Consequence

PLXNA3
NM_017514.5 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.0630

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]

PLXNA3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.991 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA3	NM_017514.5 link	c.49dupG	p.Ala17GlyfsTer39	frameshift_variant	Exon 2 of 33	ENST00000369682.4	NP_059984.3	P51805
PLXNA3	XM_047442247.1 link	c.49dupG	p.Ala17GlyfsTer39	frameshift_variant	Exon 2 of 22		XP_047298203.1
PLXNA3	XR_007068193.1 link	n.224dupG		non_coding_transcript_exon_variant	Exon 2 of 32
PLXNA3	XR_430556.4 link	n.224dupG		non_coding_transcript_exon_variant	Exon 2 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA3	ENST00000369682.4 link	c.49dupG	p.Ala17GlyfsTer39	frameshift_variant	Exon 2 of 33	1	NM_017514.5	ENSP00000358696.3		P51805
PLXNA3	ENST00000495040.1 link	n.146-867dupG		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33620

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000620

AC:

AN:

1080797

Hom.:

Cov.:

AF XY:

0.00000849

AC XY:

AN XY:

353511

show subpopulations

Gnomad4 AFR exome

AF:

0.0000384

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000374

Gnomad4 FIN exome

AF:

0.000230

Gnomad4 NFE exome

AF:

0.0000640

Gnomad4 OTH exome

AF:

0.0000220

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

111178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33620

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLXNA3-related disorder

Uncertain:1

Jan 24, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The PLXNA3 c.49dupG variant is predicted to result in a frameshift and premature protein termination (p.Ala17Glyfs*39). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.073% of alleles in individuals of African 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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over