Genetic Variant MXRA5:p.Arg2615His (chrX-3310359-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015419.4(MXRA5):c.7844G>A(p.Arg2615His) variant causes a missense change. The variant allele was found at a frequency of 0.00000167 in 1,201,086 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2615C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000093 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MXRA5
NM_015419.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

Publications

0 publications found

Variant links:

Genes affected

MXRA5 (HGNC:7539): (matrix remodeling associated 5) This gene encodes one of the matrix-remodelling associated proteins. This protein contains 7 leucine-rich repeats and 12 immunoglobulin-like C2-type domains related to perlecan. This gene has a pseudogene on chromosome Y. [provided by RefSeq, Mar 2010]

MXRA5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015419.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXRA5	NM_015419.4	MANE Select	c.7844G>A	p.Arg2615His	missense	Exon 7 of 7	NP_056234.2	Q9NR99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXRA5	ENST00000217939.7	TSL:5 MANE Select	c.7844G>A	p.Arg2615His	missense	Exon 7 of 7	ENSP00000217939.5	Q9NR99

Frequencies

GnomAD3 genomes

AF:

0.00000931

AC:

AN:

107355

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.14e-7

AC:

AN:

1093731

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

359329

show subpopulations

African (AFR)

AF:

0.0000381

AC:

AN:

26277

American (AMR)

AF:

0.00

AC:

AN:

35175

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19353

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

54045

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3971

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

838495

Other (OTH)

AF:

0.00

AC:

AN:

45919

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000931

AC:

AN:

107355

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30123

show subpopulations

African (AFR)

AF:

0.0000338

AC:

AN:

29554

American (AMR)

AF:

0.00

AC:

AN:

10142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2578

East Asian (EAS)

AF:

0.00

AC:

AN:

3342

South Asian (SAS)

AF:

0.00

AC:

AN:

2304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5535

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51576

Other (OTH)

AF:

0.00

AC:

AN:

1436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.85

MetaRNN

Uncertain

0.67

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

1.9

PhyloP100

5.0

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-4.7

REVEL

Pathogenic

0.65

Sift

Benign

0.11

Sift4G

Benign

0.066

Polyphen

1.0

Vest4

0.19

MutPred

0.72

Gain of catalytic residue at C2616 (P = 0.0272)

MVP

0.56

MPC

0.25

ClinPred

0.99

GERP RS

3.4

Varity_R

0.23

gMVP

0.69

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over