Variant chrX-3310503-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015419.4(MXRA5):c.7700C>T(p.Ala2567Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000884 in 1,198,778 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., 11 hem., cov: 19)

Exomes 𝑓: 0.000059 ( 0 hom. 18 hem. )

Consequence

MXRA5
NM_015419.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012880713).

BS2

High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA5	NM_015419.4 linkuse as main transcript	c.7700C>T	p.Ala2567Val	missense_variant	7/7	ENST00000217939.7	NP_056234.2	Q9NR99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXRA5	ENST00000217939.7 linkuse as main transcript	c.7700C>T	p.Ala2567Val	missense_variant	7/7	5	NM_015419.4	ENSP00000217939.5		Q9NR99

Frequencies

GnomAD3 genomes

AF:

0.000391

AC:

AN:

107351

Hom.:

Cov.:

AF XY:

0.000370

AC XY:

AN XY:

29735

show subpopulations

Gnomad AFR

AF:

0.00132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000294

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000193

Gnomad OTH

AF:

0.000707

GnomAD3 exomes

AF:

0.000202

AC:

AN:

167927

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

55679

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.000420

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:

0.0000272

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.0000586

AC:

AN:

1091380

Hom.:

Cov.:

AF XY:

0.0000503

AC XY:

AN XY:

357930

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

Gnomad4 AMR exome

AF:

0.000349

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000335

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000596

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000391

AC:

AN:

107398

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

AN XY:

29792

show subpopulations

Gnomad4 AFR

AF:

0.00131

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000295

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000193

Gnomad4 OTH

AF:

0.000698

Alfa

AF:

0.000364

Hom.:

Bravo

AF:

0.000529

ESP6500AA

AF:

0.00235

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000182

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.7700C>T (p.A2567V) alteration is located in exon 7 (coding exon 6) of the MXRA5 gene. This alteration results from a C to T substitution at nucleotide position 7700, causing the alanine (A) at amino acid position 2567 to be replaced by a valine (V). 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

0.080

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0050

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.70

M_CAP

Benign

0.074

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.065

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.4

REVEL

Benign

0.036

Sift

Benign

0.28

Sift4G

Uncertain

0.018

Polyphen

0.48

Vest4

0.024

MVP

0.34

MPC

0.064

ClinPred

0.0086

GERP RS

0.49

Varity_R

0.096

gMVP

0.39

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