Genetic Variant MXRA5:p.Val2617Met (chrX-3310354-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015419.4(MXRA5):c.7849G>A(p.Val2617Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,202,479 control chromosomes in the GnomAD database, including 1 homozygotes. There are 112 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 4 hem., cov: 21)

Exomes 𝑓: 0.00027 ( 1 hom. 108 hem. )

Consequence

MXRA5
NM_015419.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.479

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032521695).

BS2

High Hemizygotes in GnomAd4 at 4 gene

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.7849G>A	p.Val2617Met	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.7849G>A	p.Val2617Met	missense	Exon 7 of 7	ENSP00000217939.5	Q9NR99

Frequencies

GnomAD3 genomes

AF:

0.000192

AC:

AN:

109104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000334

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000290

Gnomad ASJ

AF:

0.00268

Gnomad EAS

AF:

0.000588

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000153

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000307

AC:

AN:

179429

AF XY:

0.000380

show subpopulations

Gnomad AFR exome

AF:

0.0000813

Gnomad AMR exome

AF:

0.0000733

Gnomad ASJ exome

AF:

0.00421

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.000678

GnomAD4 exome

AF:

0.000268

AC:

293

AN:

1093334

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

108

AN XY:

358936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26267

American (AMR)

AF:

0.0000569

AC:

AN:

35171

Ashkenazi Jewish (ASJ)

AF:

0.00413

AC:

AN:

19354

East Asian (EAS)

AF:

0.000166

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000555

AC:

AN:

54048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40310

Middle Eastern (MID)

AF:

0.000501

AC:

AN:

3992

European-Non Finnish (NFE)

AF:

0.000222

AC:

186

AN:

838060

Other (OTH)

AF:

0.000327

AC:

AN:

45926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

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:

0.000192

AC:

AN:

109145

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

31445

show subpopulations

African (AFR)

AF:

0.0000333

AC:

AN:

30045

American (AMR)

AF:

0.000290

AC:

AN:

10362

Ashkenazi Jewish (ASJ)

AF:

0.00268

AC:

AN:

2611

East Asian (EAS)

AF:

0.000590

AC:

AN:

3387

South Asian (SAS)

AF:

0.00

AC:

AN:

2405

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.000153

AC:

AN:

52296

Other (OTH)

AF:

0.00

AC:

AN:

1489

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.00105

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000300

AC:

ExAC

AF:

0.000322

AC:

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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0057

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.1

PhyloP100

0.48

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.43

Sift

Uncertain

0.021

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.21

MVP

0.39

MPC

0.39

ClinPred

0.038

GERP RS

3.3

Varity_R

0.18

gMVP

0.43

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over