Variant X-3310390-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015419.4(MXRA5):c.7813G>A(p.Gly2605Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,203,052 control chromosomes in the GnomAD database, including 23 homozygotes. There are 442 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 10 hom., 196 hem., cov: 19)

Exomes 𝑓: 0.00085 ( 13 hom. 246 hem. )

Consequence

MXRA5
NM_015419.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0200

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011803716).

BP6

Variant X-3310390-C-T is Benign according to our data. Variant chrX-3310390-C-T is described in ClinVar as [Benign]. Clinvar id is 777781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0086 (932/108314) while in subpopulation AFR AF= 0.0286 (855/29877). AF 95% confidence interval is 0.027. There are 10 homozygotes in gnomad4. There are 196 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA5	NM_015419.4 linkuse as main transcript	c.7813G>A	p.Gly2605Ser	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.7813G>A	p.Gly2605Ser	missense_variant	7/7	5	NM_015419.4	ENSP00000217939.5		Q9NR99

Frequencies

GnomAD3 genomes

AF:

0.00861

AC:

932

AN:

108270

Hom.:

Cov.:

AF XY:

0.00641

AC XY:

196

AN XY:

30572

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00451

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:

0.000135

Gnomad OTH

AF:

0.00762

GnomAD3 exomes

AF:

0.00196

AC:

334

AN:

170317

Hom.:

AF XY:

0.000991

AC XY:

AN XY:

59515

show subpopulations

Gnomad AFR exome

AF:

0.0264

Gnomad AMR exome

AF:

0.00123

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:

0.0000670

Gnomad OTH exome

AF:

0.000715

GnomAD4 exome

AF:

0.000847

AC:

927

AN:

1094738

Hom.:

Cov.:

AF XY:

0.000682

AC XY:

246

AN XY:

360482

show subpopulations

Gnomad4 AFR exome

AF:

0.0267

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000762

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00860

AC:

932

AN:

108314

Hom.:

Cov.:

AF XY:

0.00640

AC XY:

196

AN XY:

30624

show subpopulations

Gnomad4 AFR

AF:

0.0286

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000135

Gnomad4 OTH

AF:

0.00751

Alfa

AF:

0.00322

Hom.:

ESP6500AA

AF:

0.0225

AC:

ESP6500EA

AF:

0.000151

AC:

ExAC

AF:

0.00210

AC:

254

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.052

DANN

Benign

0.39

DEOGEN2

Benign

0.0010

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.60

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.46

MutationAssessor

Benign

-0.96

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.54

REVEL

Benign

0.24

Sift

Benign

0.74

Sift4G

Benign

0.88

Polyphen

0.082

Vest4

0.056

MVP

0.47

MPC

0.066

ClinPred

0.0025

GERP RS

-0.32

Varity_R

0.051

gMVP

0.29

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