Variant 5-79989217-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000512528.3(MTX3):c.256G>A(p.Ala86Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,354 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A86G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MTX3
ENST00000512528.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32685536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTX3	NM_001363818.2 linkuse as main transcript	c.256G>A	p.Ala86Thr	missense_variant	4/9	ENST00000512528.3	NP_001350747.1
MTX3	NM_001167741.2 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	3/8		NP_001161213.1
MTX3	NM_001010891.5 linkuse as main transcript	c.256G>A	p.Ala86Thr	missense_variant	4/8		NP_001010891.4
MTX3	XM_017009440.2 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	3/7		XP_016864929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTX3	ENST00000512528.3 linkuse as main transcript	c.256G>A	p.Ala86Thr	missense_variant	4/9	1	NM_001363818.2	ENSP00000424798	P3	Q5HYI7-1
MTX3	ENST00000509852.6 linkuse as main transcript	c.256G>A	p.Ala86Thr	missense_variant	4/8	1		ENSP00000423302	A1	Q5HYI7-4
MTX3	ENST00000512560.5 linkuse as main transcript	c.73G>A	p.Ala25Thr	missense_variant	3/8	2		ENSP00000423600		Q5HYI7-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453354

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722264

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 16, 2023

The c.73G>A (p.A25T) alteration is located in exon 3 (coding exon 2) of the MTX3 gene. This alteration results from a G to A substitution at nucleotide position 73, causing the alanine (A) at amino acid position 25 to be replaced by a threonine (T). 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

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

.;T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.3

M;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.8

.;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.024

.;D;T;D

Sift4G

Uncertain

0.031

D;D;D;T

Polyphen

0.40, 1.0

.;B;.;D

Vest4

0.47

MutPred

0.61

Loss of stability (P = 0.0965);Loss of stability (P = 0.0965);.;Loss of stability (P = 0.0965);

MVP

0.50

MPC

0.030

ClinPred

0.97

GERP RS

4.5

Varity_R

0.43

gMVP

0.52

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