Genetic Variant MXRA5:p.Ala2622Thr (chrX-3310339-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_015419.4(MXRA5):c.7864G>A(p.Ala2622Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,199,384 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A2622A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Consequence

MXRA5
NM_015419.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 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.7864G>A	p.Ala2622Thr	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.7864G>A	p.Ala2622Thr	missense	Exon 7 of 7	ENSP00000217939.5	Q9NR99

Frequencies

GnomAD3 genomes

AF:

0.0000183

AC:

AN:

109562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000959

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

GnomAD2 exomes

AF:

0.0000111

AC:

AN:

180209

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000732

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1089822

Hom.:

Cov.:

AF XY:

0.00000562

AC XY:

AN XY:

355590

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26139

American (AMR)

AF:

0.0000569

AC:

AN:

35124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19318

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

53952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4013

European-Non Finnish (NFE)

AF:

0.0000120

AC:

AN:

834942

Other (OTH)

AF:

0.00

AC:

AN:

45826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.0000183

AC:

AN:

109562

Hom.:

Cov.:

AF XY:

0.0000628

AC XY:

AN XY:

31822

show subpopulations

African (AFR)

AF:

0.0000332

AC:

AN:

30127

American (AMR)

AF:

0.0000959

AC:

AN:

10429

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2619

East Asian (EAS)

AF:

0.00

AC:

AN:

3422

South Asian (SAS)

AF:

0.00

AC:

AN:

2450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5775

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52376

Other (OTH)

AF:

0.00

AC:

AN:

1463

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0095

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.7

PhyloP100

2.4

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.38

Sift

Uncertain

0.027

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.19

MutPred

0.61

Loss of methylation at R2619 (P = 0.1104)

MVP

0.44

MPC

0.38

ClinPred

0.74

GERP RS

4.2

Varity_R

0.20

gMVP

0.58

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

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