Genetic Variant PLXNB3:p.Asp160Asp (chrX-153767307-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_005393.3(PLXNB3):c.480C>T(p.Asp160Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,204,718 control chromosomes in the GnomAD database, including 34 homozygotes. There are 1,543 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 17 hom., 442 hem., cov: 25)

Exomes 𝑓: 0.0033 ( 17 hom. 1101 hem. )

Consequence

PLXNB3
NM_005393.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.194

Publications

0 publications found

Variant links:

Genes affected

PLXNB3 (HGNC:9105): (plexin B3) The protein encoded by this gene is a member of the plexin family. It functions as a receptor for semaphorin 5A, and plays a role in axon guidance, invasive growth and cell migration. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

PLXNB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-153767307-C-T is Benign according to our data. Variant chrX-153767307-C-T is described in ClinVar as Benign. ClinVar VariationId is 784437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.194 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.013 (1470/112978) while in subpopulation AFR AF = 0.0418 (1304/31174). AF 95% confidence interval is 0.0399. There are 17 homozygotes in GnomAd4. There are 442 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNB3	NM_005393.3 link	c.480C>T	p.Asp160Asp	synonymous_variant	Exon 3 of 36	ENST00000361971.10	NP_005384.2	Q9ULL4-1A8K920
PLXNB3	NM_001163257.2 link	c.549C>T	p.Asp183Asp	synonymous_variant	Exon 4 of 37		NP_001156729.1	Q9ULL4-2A8K920

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNB3	ENST00000361971.10 link	c.480C>T	p.Asp160Asp	synonymous_variant	Exon 3 of 36	1	NM_005393.3	ENSP00000355378.5		Q9ULL4-1
PLXNB3	ENST00000538966.5 link	c.549C>T	p.Asp183Asp	synonymous_variant	Exon 4 of 37	5		ENSP00000442736.1		Q9ULL4-2

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1462

AN:

112926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00443

Gnomad ASJ

AF:

0.00829

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00142

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.00459

GnomAD2 exomes

AF:

0.00486

AC:

787

AN:

161937

AF XY:

0.00332

show subpopulations

Gnomad AFR exome

AF:

0.0429

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00790

Gnomad EAS exome

AF:

0.0000777

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00139

Gnomad OTH exome

AF:

0.00568

GnomAD4 exome

AF:

0.00333

AC:

3637

AN:

1091740

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

1101

AN XY:

358632

show subpopulations

African (AFR)

AF:

0.0429

AC:

1129

AN:

26329

American (AMR)

AF:

0.00378

AC:

131

AN:

34654

Ashkenazi Jewish (ASJ)

AF:

0.00925

AC:

178

AN:

19234

East Asian (EAS)

AF:

0.0000334

AC:

AN:

29969

South Asian (SAS)

AF:

0.00111

AC:

AN:

53178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39125

Middle Eastern (MID)

AF:

0.0160

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.00219

AC:

1834

AN:

839337

Other (OTH)

AF:

0.00522

AC:

239

AN:

45789

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

161

322

484

645

806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.0130

AC:

1470

AN:

112978

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

442

AN XY:

35152

show subpopulations

African (AFR)

AF:

0.0418

AC:

1304

AN:

31174

American (AMR)

AF:

0.00442

AC:

AN:

10849

Ashkenazi Jewish (ASJ)

AF:

0.00829

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3550

South Asian (SAS)

AF:

0.00142

AC:

AN:

2810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6299

Middle Eastern (MID)

AF:

0.00922

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00156

AC:

AN:

53203

Other (OTH)

AF:

0.00453

AC:

AN:

1544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

102

152

203

254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00723

Hom.:

Bravo

AF:

0.0152

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.16

(source)

DANN

Benign

0.91

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over