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

Variant summary

Our verdict is Likely benign. Variant got -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

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MXRA5	NM_015419.4 link	c.7864G>A	p.Ala2622Thr	missense_variant	Exon 7 of 7	ENST00000217939.7	NP_056234.2	Q9NR99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MXRA5	ENST00000217939.7 link	c.7864G>A	p.Ala2622Thr	missense_variant	Exon 7 of 7	5	NM_015419.4	ENSP00000217939.5		Q9NR99

Frequencies

GnomAD3 genomes

AF:

0.0000183

AC:

AN:

109562

Hom.:

Cov.:

AF XY:

0.0000628

AC XY:

AN XY:

31822

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

GnomAD3 exomes

AF:

0.0000111

AC:

AN:

180209

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

65787

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000569

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000183

AC:

AN:

109562

Hom.:

Cov.:

AF XY:

0.0000628

AC XY:

AN XY:

31822

show subpopulations

Gnomad4 AFR

AF:

0.0000332

Gnomad4 AMR

AF:

0.0000959

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7864G>A (p.A2622T) alteration is located in exon 7 (coding exon 6) of the MXRA5 gene. This alteration results from a G to A substitution at nucleotide position 7864, causing the alanine (A) at amino acid position 2622 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.33

CADD

Benign

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over