Genetic Variant MXRA8:p.Val326Phe (chr1-1354483-C-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_032348.4(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
NM_032348.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.03

Publications

3 publications found

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:

ENSG00000304860 (HGNC:):

ENSG00000304860 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3049275.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MXRA8	NM_032348.4	MANE Select	c.976G>T	p.Val326Phe	missense	Exon 6 of 10	NP_115724.1	Q9BRK3-1
MXRA8	NM_001282585.1		c.976G>T	p.Val326Phe	missense	Exon 6 of 10	NP_001269514.1	Q9BRK3-2
MXRA8	NM_001282582.2		c.976G>T	p.Val326Phe	missense	Exon 7 of 11	NP_001269511.1	Q9BRK3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MXRA8	ENST00000309212.11	TSL:1 MANE Select	c.976G>T	p.Val326Phe	missense	Exon 6 of 10	ENSP00000307887.6	Q9BRK3-1
MXRA8	ENST00000342753.8	TSL:1	c.673G>T	p.Val225Phe	missense	Exon 5 of 9	ENSP00000344998.4	Q9BRK3-4
MXRA8	ENST00000953650.1		c.1060G>T	p.Val354Phe	missense	Exon 6 of 10	ENSP00000623709.1

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

GnomAD2 exomes

AF:

0.000778

AC:

189

AN:

242920

AF XY:

0.000634

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 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

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.0000447

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.000957

AC:

AN:

26118

East Asian (EAS)

AF:

0.00393

AC:

156

AN:

39690

South Asian (SAS)

AF:

0.000719

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.000347

AC:

AN:

51890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000639

AC:

AN:

1111764

Other (OTH)

AF:

0.000365

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000387

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41576

American (AMR)

AF:

0.000131

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00598

AC:

AN:

5182

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000462

Hom.:

Bravo

AF:

0.000419

ExAC

AF:

0.000741

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MXRA8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.6

PhyloP100

3.0

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.18

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.84

MVP

0.56

MPC

0.70

ClinPred

0.13

GERP RS

3.4

Varity_R

0.45

gMVP

0.92

Mutation Taster

=35/65

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over