Variant 7-132130556-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_020911.2(PLXNA4):c.5608C>T(p.His1870Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,614,076 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. H1870H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 20 hom. )

Consequence

PLXNA4
NM_020911.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 8.09

Variant links:

Genes affected

PLXNA4 (HGNC:9102): (plexin A4) Predicted to enable semaphorin receptor activity. Predicted to be involved in several processes, including axon guidance; positive regulation of axonogenesis; and regulation of GTPase activity. Predicted to act upstream of or within several processes, including nervous system development; regulation of axon extension involved in axon guidance; and regulation of negative chemotaxis. Predicted to be located in plasma membrane. Predicted to be part of semaphorin receptor complex. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLXNA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074129403).

BP6

Variant 7-132130556-G-A is Benign according to our data. Variant chr7-132130556-G-A is described in ClinVar as [Benign]. Clinvar id is 3041401.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 463 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA4	NM_020911.2 linkuse as main transcript	c.5608C>T	p.His1870Tyr	missense_variant	32/32	ENST00000321063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA4	ENST00000321063.9 linkuse as main transcript	c.5608C>T	p.His1870Tyr	missense_variant	32/32	5	NM_020911.2	P1	Q9HCM2-1
PLXNA4	ENST00000359827.7 linkuse as main transcript	c.5608C>T	p.His1870Tyr	missense_variant	32/32	5		P1	Q9HCM2-1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

464

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00372

AC:

928

AN:

249198

Hom.:

AF XY:

0.00410

AC XY:

554

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00835

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00732

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00389

Gnomad OTH exome

AF:

0.00611

GnomAD4 exome

AF:

0.00345

AC:

5038

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

2633

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00340

Gnomad4 ASJ exome

AF:

0.00915

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00722

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.00321

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.00304

AC:

463

AN:

152248

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

228

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000867

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00415

Hom.:

Bravo

AF:

0.00331

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000743

AC:

ESP6500EA

AF:

0.00516

AC:

ExAC

AF:

0.00340

AC:

411

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00611

EpiControl

AF:

0.00587

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLXNA4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

0.092

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.71

T;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.16

B;B

Vest4

0.28

MVP

0.10

MPC

0.77

ClinPred

0.021

GERP RS

5.5

Varity_R

0.14

gMVP

0.12

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