Genetic Variant MXRA8:p.Gly382Trp (chr1-1354194-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032348.4(MXRA8):c.1144G>T(p.Gly382Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G382R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MXRA8
NM_032348.4 missense, splice_region

Scores

Splicing: ADA: 0.0001072

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.405

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17806348).

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.1144G>T	p.Gly382Trp	missense splice_region	Exon 7 of 10	NP_115724.1	Q9BRK3-1
MXRA8	NM_001282585.1		c.1144G>T	p.Gly382Trp	missense splice_region	Exon 7 of 10	NP_001269514.1	Q9BRK3-2
MXRA8	NM_001282582.2		c.1144G>T	p.Gly382Trp	missense splice_region	Exon 8 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.1144G>T	p.Gly382Trp	missense splice_region	Exon 7 of 10	ENSP00000307887.6	Q9BRK3-1
MXRA8	ENST00000342753.8	TSL:1	c.841G>T	p.Gly281Trp	missense splice_region	Exon 6 of 9	ENSP00000344998.4	Q9BRK3-4
MXRA8	ENST00000474033.5	TSL:1	n.71G>T		splice_region non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111948

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.017

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.77

M_CAP

Benign

0.070

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.41

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.029

Sift

Uncertain

0.015

Sift4G

Benign

0.19

Polyphen

0.11

Vest4

0.46

MutPred

0.33

Loss of disorder (P = 0.0114)

MVP

0.26

MPC

0.61

ClinPred

0.33

GERP RS

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.32

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.080

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over