chr3-126988613-G-T

Position:

chr3-126988613-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2

The NM_032242.4(PLXNA1):c.20G>T(p.Ser7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,553,174 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00036 ( 5 hom. )

Consequence

PLXNA1
NM_032242.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.18

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 -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PLXNA1. . Gene score misZ 3.4482 (greater than the threshold 3.09). Trascript score misZ 4.1522 (greater than threshold 3.09). GenCC has associacion of gene with Dworschak-Punetha neurodevelopmental syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.008778155).

BP6

Variant 3-126988613-G-T is Benign according to our data. Variant chr3-126988613-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 778111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000322 (49/152366) while in subpopulation SAS AF= 0.00352 (17/4834). AF 95% confidence interval is 0.00224. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA1	NM_032242.4 linkuse as main transcript	c.20G>T	p.Ser7Ile	missense_variant	2/32	ENST00000393409.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA1	ENST00000393409.3 linkuse as main transcript	c.20G>T	p.Ser7Ile	missense_variant	2/32	1	NM_032242.4	P1
PLXNA1	ENST00000684469.1 linkuse as main transcript	c.20G>T	p.Ser7Ile	missense_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000605

AC:

110

AN:

181876

Hom.:

AF XY:

0.000680

AC XY:

AN XY:

98538

show subpopulations

Gnomad AFR exome

AF:

0.0000843

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.0000650

Gnomad SAS exome

AF:

0.00277

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.00154

GnomAD4 exome

AF:

0.000365

AC:

511

AN:

1400808

Hom.:

Cov.:

AF XY:

0.000450

AC XY:

311

AN XY:

690850

show subpopulations

Gnomad4 AFR exome

AF:

0.0000623

Gnomad4 AMR exome

AF:

0.0000531

Gnomad4 ASJ exome

AF:

0.00373

Gnomad4 EAS exome

AF:

0.0000520

Gnomad4 SAS exome

AF:

0.00300

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.000709

GnomAD4 genome

AF:

0.000322

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000642

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000474

AC:

ExAC

AF:

0.000593

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

PLXNA1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 26, 2019

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 30, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.14

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.43

M_CAP

Benign

0.031

MetaRNN

Benign

0.0088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.93

REVEL

Benign

0.074

Sift

Uncertain

0.026

Sift4G

Uncertain

0.050

Vest4

0.30

MVP

0.23

MPC

0.84

ClinPred

0.0098

GERP RS

1.3

Varity_R

0.078

gMVP

0.53

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