Genetic Variant NM_017514.5:c.49delG (chrX-154460224-TG-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. 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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0630

Publications

6 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017514.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA3	NM_017514.5	MANE Select	c.49delG	p.Ala17ProfsTer12	frameshift	Exon 2 of 33	NP_059984.3	P51805

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLXNA3	ENST00000369682.4	TSL:1 MANE Select	c.49delG	p.Ala17ProfsTer12	frameshift	Exon 2 of 33	ENSP00000358696.3	P51805
PLXNA3	ENST00000937806.1		c.49delG	p.Ala17ProfsTer12	frameshift	Exon 2 of 33	ENSP00000607865.1
PLXNA3	ENST00000955276.1		c.49delG	p.Ala17ProfsTer12	frameshift	Exon 2 of 33	ENSP00000625335.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111180

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000178

AC:

AN:

168147

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000405

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000368

AC:

AN:

1085745

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

356251

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26153

American (AMR)

AF:

0.00

AC:

AN:

35045

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19219

East Asian (EAS)

AF:

0.00

AC:

AN:

30064

South Asian (SAS)

AF:

0.00

AC:

AN:

53620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39225

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3885

European-Non Finnish (NFE)

AF:

0.00000480

AC:

AN:

832869

Other (OTH)

AF:

0.00

AC:

AN:

45665

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33622

African (AFR)

AF:

0.00

AC:

AN:

30598

American (AMR)

AF:

0.00

AC:

AN:

10605

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2613

East Asian (EAS)

AF:

0.00

AC:

AN:

3544

South Asian (SAS)

AF:

0.00

AC:

AN:

2674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

233

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52683

Other (OTH)

AF:

0.00

AC:

AN:

1486

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.063

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over