Variant X-3310612-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015419.4(MXRA5):c.7591C>G(p.Leu2531Val) variant causes a missense change. The variant allele was found at a frequency of 0.287 in 741,700 control chromosomes in the GnomAD database, including 44,032 homozygotes. There are 76,223 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.43 ( 8279 hom., 2186 hem., cov: 14)

Exomes 𝑓: 0.29 ( 44032 hom. 76223 hem. )

Failed GnomAD Quality Control

Consequence

MXRA5
NM_015419.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.96

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004083544).

BP6

Variant X-3310612-G-C is Benign according to our data. Variant chrX-3310612-G-C is described in ClinVar as [Benign]. Clinvar id is 769169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA5	NM_015419.4 linkuse as main transcript	c.7591C>G	p.Leu2531Val	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.7591C>G	p.Leu2531Val	missense_variant	7/7	5	NM_015419.4	ENSP00000217939.5		Q9NR99

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

32010

AN:

75034

Hom.:

8292

Cov.:

AF XY:

0.132

AC XY:

2179

AN XY:

16456

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.424

GnomAD3 exomes

AF:

0.195

AC:

20811

AN:

106567

Hom.:

5214

AF XY:

0.242

AC XY:

8341

AN XY:

34403

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.516

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.0307

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.287

AC:

212944

AN:

741700

Hom.:

44032

Cov.:

AF XY:

0.343

AC XY:

76223

AN XY:

222530

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.690

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.443

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.426

AC:

31993

AN:

75069

Hom.:

8279

Cov.:

AF XY:

0.132

AC XY:

2186

AN XY:

16503

show subpopulations

Gnomad4 AFR

AF:

0.343

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.458

Gnomad4 EAS

AF:

0.618

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.311

Hom.:

1860

ExAC

AF:

0.000723

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.3

DANN

Benign

0.077

DEOGEN2

Benign

0.028

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.071

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.6

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.61

PROVEAN

Benign

2.9

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.047

MPC

0.063

ClinPred

0.0044

GERP RS

3.9

Varity_R

0.059

gMVP

0.36

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