Variant 5-79985644-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_001363818.2(MTX3):c.755G>A(p.Gly252Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000417 in 1,611,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

MTX3
NM_001363818.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

Variant links:

Genes affected

MTX3 (HGNC:24812): (metaxin 3) Predicted to be involved in mitochondrion organization. Part of MIB complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

MTX3 links:

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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=0.123119086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTX3	NM_001363818.2 linkuse as main transcript	c.755G>A	p.Gly252Glu	missense_variant	8/9	ENST00000512528.3	NP_001350747.1
MTX3	NM_001167741.2 linkuse as main transcript	c.572G>A	p.Gly191Glu	missense_variant	7/8		NP_001161213.1	Q5HYI7-5
MTX3	NM_001010891.5 linkuse as main transcript	c.739+1306G>A		intron_variant			NP_001010891.4	Q5HYI7-4
MTX3	XM_017009440.2 linkuse as main transcript	c.556+1306G>A		intron_variant			XP_016864929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTX3	ENST00000512528.3 linkuse as main transcript	c.755G>A	p.Gly252Glu	missense_variant	8/9	1	NM_001363818.2	ENSP00000424798.2	Q5HYI7-1
MTX3	ENST00000509852.6 linkuse as main transcript	c.739+1306G>A		intron_variant		1		ENSP00000423302.1	Q5HYI7-4
MTX3	ENST00000512560.5 linkuse as main transcript	c.572G>A	p.Gly191Glu	missense_variant	7/8	2		ENSP00000423600.1	Q5HYI7-5

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000403

AC:

100

AN:

248394

Hom.:

AF XY:

0.000430

AC XY:

AN XY:

134738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000781

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000417

AC:

609

AN:

1459888

Hom.:

Cov.:

AF XY:

0.000402

AC XY:

292

AN XY:

726270

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000500

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000414

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000740

Hom.:

Bravo

AF:

0.000374

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000490

AC:

ExAC

AF:

0.000414

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000534

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

Oct 05, 2021

The c.572G>A (p.G191E) alteration is located in exon 7 (coding exon 6) of the MTX3 gene. This alteration results from a G to A substitution at nucleotide position 572, causing the glycine (G) at amino acid position 191 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0045

T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.99

D;.

Vest4

0.42

MVP

0.59

MPC

0.22

ClinPred

0.17

GERP RS

6.1

Varity_R

0.18

gMVP

0.62

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