Variant 1-1354483-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000309212.11(MXRA8):c.976G>T(p.Val326Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,612,250 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

MXRA8
ENST00000309212.11 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.03

Variant links:

Genes affected

MXRA8 (HGNC:7542): (matrix remodeling associated 8) Predicted to be involved in establishment of glial blood-brain barrier. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MXRA8 links:

MXRA8 (HGNC:):

MXRA8 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=0.038724035).

BP6

Variant 1-1354483-C-A is Benign according to our data. Variant chr1-1354483-C-A is described in ClinVar as [Benign]. Clinvar id is 3049275.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA8	NM_032348.4 linkuse as main transcript	c.976G>T	p.Val326Phe	missense_variant	6/10	ENST00000309212.11	NP_115724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXRA8	ENST00000309212.11 linkuse as main transcript	c.976G>T	p.Val326Phe	missense_variant	6/10	1	NM_032348.4	ENSP00000307887.6		Q9BRK3-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00597

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000778

AC:

189

AN:

242920

Hom.:

AF XY:

0.000634

AC XY:

AN XY:

132420

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00102

Gnomad EAS exome

AF:

0.00718

Gnomad SAS exome

AF:

0.000590

Gnomad FIN exome

AF:

0.000556

Gnomad NFE exome

AF:

0.000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000244

AC:

356

AN:

1459928

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

187

AN XY:

726242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00393

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.000347

Gnomad4 NFE exome

AF:

0.0000639

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000387

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00598

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000441

Hom.:

Bravo

AF:

0.000419

ExAC

AF:

0.000741

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MXRA8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 18, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

.;T;.;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.6

.;M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.9

D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.99, 0.99

.;D;D;.

Vest4

0.84

MVP

0.56

MPC

0.70

ClinPred

0.13

GERP RS

3.4

Varity_R

0.45

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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