Genetic Variant MXRA5:p.Asn2675Ser (chrX-3310179-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015419.4(MXRA5):c.8024A>G(p.Asn2675Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,209,731 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 99 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.00023 ( 0 hom. 88 hem. )

Consequence

MXRA5
NM_015419.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.188

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008993685).

BP6

Variant X-3310179-T-C is Benign according to our data. Variant chrX-3310179-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2659875.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 11 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.8024A>G	p.Asn2675Ser	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.8024A>G	p.Asn2675Ser	missense	Exon 7 of 7	ENSP00000217939.5	Q9NR99

Frequencies

GnomAD3 genomes

AF:

0.000385

AC:

AN:

111576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000489

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000940

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:

0.000510

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000202

AC:

AN:

183092

AF XY:

0.000177

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000226

AC:

248

AN:

1098098

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

363472

show subpopulations

African (AFR)

AF:

0.000530

AC:

AN:

26402

American (AMR)

AF:

0.0000568

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19377

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40479

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000265

AC:

223

AN:

842077

Other (OTH)

AF:

0.000152

AC:

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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:

0.000385

AC:

AN:

111633

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

33859

show subpopulations

African (AFR)

AF:

0.000488

AC:

AN:

30754

American (AMR)

AF:

0.0000939

AC:

AN:

10647

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3502

South Asian (SAS)

AF:

0.00

AC:

AN:

2595

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.000510

AC:

AN:

52966

Other (OTH)

AF:

0.00

AC:

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000608

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.024

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.0031

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.72

M_CAP

Benign

0.0064

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

-0.19

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.060

REVEL

Benign

0.11

Sift

Benign

0.87

Sift4G

Benign

0.95

Polyphen

0.0020

Vest4

0.10

MVP

0.23

MPC

0.060

ClinPred

0.013

GERP RS

-7.8

Varity_R

0.020

gMVP

0.21

Mutation Taster

=100/0

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

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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