Variant chr17-76710628-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198530.4(MXRA7):c.319G>A(p.Glu107Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,383,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

MXRA7
NM_198530.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0110

Variant links:

Genes affected

MXRA7 (HGNC:7541): (matrix remodeling associated 7) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

MXRA7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11130592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MXRA7	NM_198530.4 linkuse as main transcript	c.319G>A	p.Glu107Lys	missense_variant	1/4	ENST00000449428.7	NP_940932.2
MXRA7	NM_001008528.3 linkuse as main transcript	c.319G>A	p.Glu107Lys	missense_variant	1/4		NP_001008528.1
MXRA7	NM_001008529.3 linkuse as main transcript	c.319G>A	p.Glu107Lys	missense_variant	1/5		NP_001008529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXRA7	ENST00000449428.7 linkuse as main transcript	c.319G>A	p.Glu107Lys	missense_variant	1/4	1	NM_198530.4	ENSP00000391466	P2	P84157-2
MXRA7	ENST00000355797.7 linkuse as main transcript	c.319G>A	p.Glu107Lys	missense_variant	1/4	2		ENSP00000348050	A2	P84157-1
MXRA7	ENST00000375036.6 linkuse as main transcript	c.319G>A	p.Glu107Lys	missense_variant	1/5	2		ENSP00000364176	A2	P84157-3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000167

AC:

AN:

59834

Hom.:

AF XY:

0.0000286

AC XY:

AN XY:

34920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000470

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000487

AC:

AN:

1232030

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

605874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000771

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000401

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74046

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000375

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

Feb 12, 2024

The c.319G>A (p.E107K) alteration is located in exon 1 (coding exon 1) of the MXRA7 gene. This alteration results from a G to A substitution at nucleotide position 319, causing the glutamic acid (E) at amino acid position 107 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0065

T;.;.

Eigen

Benign

-0.029

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

0.92

N;N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.059

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.081

MutPred

0.35

Gain of ubiquitination at E107 (P = 0.0051);Gain of ubiquitination at E107 (P = 0.0051);Gain of ubiquitination at E107 (P = 0.0051);

MVP

0.21

MPC

0.11

ClinPred

0.22

GERP RS

3.4

Varity_R

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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