Genetic Variant NM_017514.5:c.42G>C (chrX-154460225-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_017514.5(PLXNA3):c.42G>C(p.Val14Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,193,228 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.000023 ( 0 hom. 10 hem. )

Consequence

PLXNA3
NM_017514.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0630

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-154460225-G-C is Benign according to our data. Variant chrX-154460225-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3030538.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.063 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

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.42G>C	p.Val14Val	synonymous	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.42G>C	p.Val14Val	synonymous	Exon 2 of 33	ENSP00000358696.3	P51805
PLXNA3	ENST00000937806.1		c.42G>C	p.Val14Val	synonymous	Exon 2 of 33	ENSP00000607865.1
PLXNA3	ENST00000955276.1		c.42G>C	p.Val14Val	synonymous	Exon 2 of 33	ENSP00000625335.1

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111498

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000939

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:

0.0000957

AC:

AN:

167182

AF XY:

0.000102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000496

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000482

GnomAD4 exome

AF:

0.0000231

AC:

AN:

1081730

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

351586

show subpopulations

African (AFR)

AF:

0.0000767

AC:

AN:

26091

American (AMR)

AF:

0.000543

AC:

AN:

35011

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19168

East Asian (EAS)

AF:

0.00

AC:

AN:

30084

South Asian (SAS)

AF:

0.0000187

AC:

AN:

53521

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38963

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3860

European-Non Finnish (NFE)

AF:

0.00000362

AC:

AN:

829525

Other (OTH)

AF:

0.00

AC:

AN:

45507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.00000897

AC:

AN:

111498

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30676

American (AMR)

AF:

0.0000939

AC:

AN:

10647

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2627

East Asian (EAS)

AF:

0.00

AC:

AN:

3553

South Asian (SAS)

AF:

0.00

AC:

AN:

2707

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6111

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52778

Other (OTH)

AF:

0.00

AC:

AN:

1491

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PLXNA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.68

PhyloP100

0.063

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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