Variant 3-126988659-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_032242.4(PLXNA1):c.66G>A(p.Pro22Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,578,662 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00049 ( 2 hom. )

Consequence

PLXNA1
NM_032242.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.836

Variant links:

Genes affected

PLXNA1 (HGNC:9099): (plexin A1) Predicted to enable semaphorin receptor activity. Predicted to be involved in several processes, including generation of neurons; regulation of GTPase activity; and regulation of cell shape. Predicted to act upstream of or within dichotomous subdivision of terminal units involved in salivary gland branching; neuron projection morphogenesis; and regulation of smooth muscle cell migration. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLXNA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-126988659-G-A is Benign according to our data. Variant chr3-126988659-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052460.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.836 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000525 (80/152318) while in subpopulation NFE AF= 0.000441 (30/68018). AF 95% confidence interval is 0.000317. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA1	NM_032242.4 linkuse as main transcript	c.66G>A	p.Pro22Pro	synonymous_variant	2/32	ENST00000393409.3	NP_115618.3	Q9UIW2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA1	ENST00000393409.3 linkuse as main transcript	c.66G>A	p.Pro22Pro	synonymous_variant	2/32	1	NM_032242.4	ENSP00000377061.2		Q9UIW2
PLXNA1	ENST00000684469.1 linkuse as main transcript	c.66G>A	p.Pro22Pro	synonymous_variant	2/2			ENSP00000507976.1		A0A804HKL4

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000532

AC:

115

AN:

215972

Hom.:

AF XY:

0.000556

AC XY:

AN XY:

116838

show subpopulations

Gnomad AFR exome

AF:

0.000479

Gnomad AMR exome

AF:

0.000227

Gnomad ASJ exome

AF:

0.00534

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000835

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000586

Gnomad OTH exome

AF:

0.000568

GnomAD4 exome

AF:

0.000488

AC:

696

AN:

1426344

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

341

AN XY:

705694

show subpopulations

Gnomad4 AFR exome

AF:

0.000367

Gnomad4 AMR exome

AF:

0.000243

Gnomad4 ASJ exome

AF:

0.00541

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000175

Gnomad4 FIN exome

AF:

0.0000395

Gnomad4 NFE exome

AF:

0.000462

Gnomad4 OTH exome

AF:

0.000391

GnomAD4 genome

AF:

0.000525

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.000586

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLXNA1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.7

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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