Genetic Variant NM_017514.5:c.3723C>G (chrX-154467904-C-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_017514.5(PLXNA3):c.3723C>G(p.Ala1241Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 20856 hom., 22396 hem., cov: 23)

Exomes 𝑓: 0.83 ( 263980 hom. 299405 hem. )

Failed GnomAD Quality Control

Consequence

PLXNA3
NM_017514.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Publications

9 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant X-154467904-C-G is Benign according to our data. Variant chrX-154467904-C-G is described in ClinVar as Benign. ClinVar VariationId is 769207.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.25 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA3	NM_017514.5	MANE Select	c.3723C>G	p.Ala1241Ala	synonymous	Exon 21 of 33	NP_059984.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLXNA3	ENST00000369682.4	TSL:1 MANE Select	c.3723C>G	p.Ala1241Ala	synonymous	Exon 21 of 33	ENSP00000358696.3
PLXNA3	ENST00000937806.1		c.3684C>G	p.Ala1228Ala	synonymous	Exon 21 of 33	ENSP00000607865.1
PLXNA3	ENST00000955276.1		c.3633C>G	p.Ala1211Ala	synonymous	Exon 21 of 33	ENSP00000625335.1

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

75133

AN:

110553

Hom.:

20857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.873

Gnomad AMR

AF:

0.835

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.897

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.864

Gnomad OTH

AF:

0.678

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.835

AC:

915391

AN:

1096729

Hom.:

263980

Cov.:

AF XY:

0.825

AC XY:

299405

AN XY:

362733

show subpopulations

African (AFR)

AF:

0.232

AC:

6130

AN:

26393

American (AMR)

AF:

0.902

AC:

31735

AN:

35177

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

13637

AN:

19376

East Asian (EAS)

AF:

0.903

AC:

27282

AN:

30198

South Asian (SAS)

AF:

0.567

AC:

30703

AN:

54122

European-Finnish (FIN)

AF:

0.895

AC:

35282

AN:

39407

Middle Eastern (MID)

AF:

0.592

AC:

2449

AN:

4134

European-Non Finnish (NFE)

AF:

0.870

AC:

732061

AN:

841857

Other (OTH)

AF:

0.784

AC:

36112

AN:

46065

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

5864

11727

17591

23454

29318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19918

39836

59754

79672

99590

<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: InbreedingCoeff

AF:

0.680

AC:

75162

AN:

110609

Hom.:

20856

Cov.:

AF XY:

0.681

AC XY:

22396

AN XY:

32865

show subpopulations

African (AFR)

AF:

0.253

AC:

7724

AN:

30547

American (AMR)

AF:

0.836

AC:

8768

AN:

10492

Ashkenazi Jewish (ASJ)

AF:

0.710

AC:

1872

AN:

2635

East Asian (EAS)

AF:

0.848

AC:

2931

AN:

3458

South Asian (SAS)

AF:

0.542

AC:

1423

AN:

2624

European-Finnish (FIN)

AF:

0.897

AC:

5245

AN:

5845

Middle Eastern (MID)

AF:

0.653

AC:

141

AN:

216

European-Non Finnish (NFE)

AF:

0.864

AC:

45450

AN:

52621

Other (OTH)

AF:

0.682

AC:

1025

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

598

1195

1793

2390

2988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.760

Hom.:

9557

Bravo

AF:

0.666

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.3

(source)

PhyloP100

1.2

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over