Variant 17-76710868-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.79G>A(p.Val27Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 987,676 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

MXRA7
NM_198530.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.32

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=0.10374391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MXRA7	NM_198530.4 linkuse as main transcript	c.79G>A	p.Val27Met	missense_variant	1/4	ENST00000449428.7	NP_940932.2
MXRA7	NM_001008528.3 linkuse as main transcript	c.79G>A	p.Val27Met	missense_variant	1/4		NP_001008528.1
MXRA7	NM_001008529.3 linkuse as main transcript	c.79G>A	p.Val27Met	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.79G>A	p.Val27Met	missense_variant	1/4	1	NM_198530.4	ENSP00000391466	P2	P84157-2
MXRA7	ENST00000355797.7 linkuse as main transcript	c.79G>A	p.Val27Met	missense_variant	1/4	2		ENSP00000348050	A2	P84157-1
MXRA7	ENST00000375036.6 linkuse as main transcript	c.79G>A	p.Val27Met	missense_variant	1/5	2		ENSP00000364176	A2	P84157-3

Frequencies

GnomAD3 genomes

AF:

0.000137

AC:

AN:

146130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000491

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000832

AC:

AN:

841546

Hom.:

Cov.:

AF XY:

0.00000511

AC XY:

AN XY:

391330

show subpopulations

Gnomad4 AFR exome

AF:

0.000191

Gnomad4 AMR exome

AF:

0.00

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:

0.00000130

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000137

AC:

AN:

146130

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

AN XY:

71058

show subpopulations

Gnomad4 AFR

AF:

0.000491

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000155

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

Apr 06, 2024

The c.79G>A (p.V27M) 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 79, causing the valine (V) at amino acid position 27 to be replaced by a methionine (M). 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

Pathogenic

0.59

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0085

T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.33

T;T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.070

N;N;N

REVEL

Benign

0.075

Sift

Uncertain

0.012

D;D;D

Sift4G

Benign

0.072

T;D;D

Polyphen

0.81

P;P;P

Vest4

0.099

MutPred

0.35

Gain of catalytic residue at V27 (P = 0.0022);Gain of catalytic residue at V27 (P = 0.0022);Gain of catalytic residue at V27 (P = 0.0022);

MVP

0.055

MPC

0.21

ClinPred

0.31

GERP RS

-2.2

Varity_R

0.052

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