chrX-154460224-TG-T

Variant names:

• chrX-154460224-TG-T
• rs782247826
• NM_017514.5:c.49delG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_017514.5(PLXNA3):​c.49delG​(p.Ala17ProfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,085,745 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.0000037 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: PLXNA3 NM_017514.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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 Likely_pathogenic. Variant got 6 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.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA3	NM_017514.5	c.49delG	p.Ala17ProfsTer12	frameshift_variant	Exon 2 of 33	ENST00000369682.4	NP_059984.3
PLXNA3	XM_047442247.1	c.49delG	p.Ala17ProfsTer12	frameshift_variant	Exon 2 of 22		XP_047298203.1
PLXNA3	XR_007068193.1	n.224delG		non_coding_transcript_exon_variant	Exon 2 of 32
PLXNA3	XR_430556.4	n.224delG		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	c.49delG	p.Ala17ProfsTer12	frameshift_variant	Exon 2 of 33	1	NM_017514.5	ENSP00000358696.3
PLXNA3	ENST00000495040.1	n.146-867delG		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 111180 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 33622 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: 0.00000368 AC: 4 AN: 1085745 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 356251

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000480

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 111180 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 33622

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs782247826; hg19: chrX-153688564;