Variant 3-48409421-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001130082.3(PLXNB1):c.5995G>C(p.Val1999Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1999M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PLXNB1
NM_001130082.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99

Variant links:

Genes affected

PLXNB1 (HGNC:9103): (plexin B1) Enables semaphorin receptor activity. Involved in several processes, including negative regulation of cell adhesion; regulation of cell shape; and semaphorin-plexin signaling pathway. Is integral component of plasma membrane. Part of semaphorin receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

PLXNB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNB1	NM_001130082.3 linkuse as main transcript	c.5995G>C	p.Val1999Leu	missense_variant	34/38	ENST00000296440.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNB1	ENST00000296440.11 linkuse as main transcript	c.5995G>C	p.Val1999Leu	missense_variant	34/38	1	NM_001130082.3	P1	O43157-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.5995G>C (p.V1999L) alteration is located in exon 34 (coding exon 32) of the PLXNB1 gene. This alteration results from a G to C substitution at nucleotide position 5995, causing the valine (V) at amino acid position 1999 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.83

D;D;D

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.70

MutPred

0.61

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;

MVP

0.56

MPC

1.4

ClinPred

0.95

GERP RS

4.6

Varity_R

0.79

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over