Variant 5-79988273-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000512528.3(MTX3):c.547A>G(p.Arg183Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,554,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MTX3
ENST00000512528.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTX3	NM_001363818.2 linkuse as main transcript	c.547A>G	p.Arg183Gly	missense_variant	6/9	ENST00000512528.3	NP_001350747.1
MTX3	NM_001167741.2 linkuse as main transcript	c.364A>G	p.Arg122Gly	missense_variant	5/8		NP_001161213.1
MTX3	NM_001010891.5 linkuse as main transcript	c.547A>G	p.Arg183Gly	missense_variant	6/8		NP_001010891.4
MTX3	XM_017009440.2 linkuse as main transcript	c.364A>G	p.Arg122Gly	missense_variant	5/7		XP_016864929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTX3	ENST00000512528.3 linkuse as main transcript	c.547A>G	p.Arg183Gly	missense_variant	6/9	1	NM_001363818.2	ENSP00000424798	P3	Q5HYI7-1
MTX3	ENST00000509852.6 linkuse as main transcript	c.547A>G	p.Arg183Gly	missense_variant	6/8	1		ENSP00000423302	A1	Q5HYI7-4
MTX3	ENST00000512560.5 linkuse as main transcript	c.364A>G	p.Arg122Gly	missense_variant	5/8	2		ENSP00000423600		Q5HYI7-5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152234

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:

0.0000176

AC:

AN:

170806

Hom.:

AF XY:

0.0000111

AC XY:

AN XY:

90466

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:

0.0000435

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1402496

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

693044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000200

Gnomad4 NFE exome

AF:

0.0000158

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

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

Jun 16, 2024

The c.364A>G (p.R122G) alteration is located in exon 5 (coding exon 4) of the MTX3 gene. This alteration results from a A to G substitution at nucleotide position 364, causing the arginine (R) at amino acid position 122 to be replaced by a glycine (G). 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

0.86

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.96

D;D;D

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.2

M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.3

D;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.87

MutPred

0.77

Loss of stability (P = 0.0131);.;Loss of stability (P = 0.0131);

MVP

0.63

MPC

0.23

ClinPred

0.94

GERP RS

3.4

Varity_R

0.92

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: 42

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