Variant chr17-76710745-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198530.4(MXRA7):c.202C>T(p.Pro68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,108,770 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

MXRA7
NM_198530.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.223

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0636155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA7	NM_198530.4 linkuse as main transcript	c.202C>T	p.Pro68Ser	missense_variant	1/4	ENST00000449428.7	NP_940932.2	P84157-2
MXRA7	NM_001008528.3 linkuse as main transcript	c.202C>T	p.Pro68Ser	missense_variant	1/4		NP_001008528.1	P84157-1
MXRA7	NM_001008529.3 linkuse as main transcript	c.202C>T	p.Pro68Ser	missense_variant	1/5		NP_001008529.1	P84157-3Q6ZR64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MXRA7	ENST00000449428.7 linkuse as main transcript	c.202C>T	p.Pro68Ser	missense_variant	1/4	1	NM_198530.4	ENSP00000391466.1	P84157-2
MXRA7	ENST00000355797.7 linkuse as main transcript	c.202C>T	p.Pro68Ser	missense_variant	1/4	2		ENSP00000348050.2	P84157-1
MXRA7	ENST00000375036.6 linkuse as main transcript	c.202C>T	p.Pro68Ser	missense_variant	1/5	2		ENSP00000364176.1	P84157-3

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

148238

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:

0.0000450

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

AN:

960532

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

452922

show subpopulations

Gnomad4 AFR exome

AF:

0.000104

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:

0.000113

Gnomad4 OTH exome

AF:

0.0000549

GnomAD4 genome

AF:

0.0000202

AC:

AN:

148238

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72268

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:

0.0000450

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Nov 28, 2024

The c.202C>T (p.P68S) alteration is located in exon 1 (coding exon 1) of the MXRA7 gene. This alteration results from a C to T substitution at nucleotide position 202, causing the proline (P) at amino acid position 68 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.9

DANN

Benign

0.89

DEOGEN2

Benign

0.054

T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.40

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.064

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L;L

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

N;D;D

REVEL

Benign

0.017

Sift

Benign

0.059

T;T;T

Sift4G

Uncertain

0.035

D;T;T

Polyphen

0.012

B;B;B

Vest4

0.071

MutPred

0.31

Gain of phosphorylation at P68 (P = 0.0039);Gain of phosphorylation at P68 (P = 0.0039);Gain of phosphorylation at P68 (P = 0.0039);

MVP

0.014

MPC

0.10

ClinPred

0.10

GERP RS

-1.0

Varity_R

0.028

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