Variant 1-1354066-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032348.4(MXRA8):c.1186G>A(p.Asp396Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,612,968 control chromosomes in the GnomAD database, including 10 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 Likely benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0034 ( 8 hom. )

Consequence

MXRA8
NM_032348.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.32

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:

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=0.006739646).

BP6

Variant 1-1354066-C-T is Benign according to our data. Variant chr1-1354066-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3034759.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA8	NM_032348.4 link	c.1186G>A	p.Asp396Asn	missense_variant	8/10	ENST00000309212.11	NP_115724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXRA8	ENST00000309212.11 link	c.1186G>A	p.Asp396Asn	missense_variant	8/10	1	NM_032348.4	ENSP00000307887.6		Q9BRK3-1

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

405

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00240

AC:

601

AN:

250424

Hom.:

AF XY:

0.00250

AC XY:

339

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00378

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00340

AC:

4969

AN:

1460622

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

2438

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00351

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000594

Gnomad4 NFE exome

AF:

0.00409

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.00270

AC:

411

AN:

152346

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00363

Hom.:

Bravo

AF:

0.00303

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00236

AC:

286

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00529

EpiControl

AF:

0.00498

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MXRA8-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 06, 2023

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

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

.;T;.;.

Eigen

Benign

0.15

Eigen_PC

Benign

-0.020

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.052

MetaRNN

Benign

0.0067

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;M;M;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.9

D;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.

Vest4

0.59

MVP

0.42

MPC

0.32

ClinPred

0.020

GERP RS

3.9

Varity_R

0.14

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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