Variant 5-79989235-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363818.2(MTX3):c.238G>A(p.Ala80Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,583,472 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MTX3
NM_001363818.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTX3	NM_001363818.2 linkuse as main transcript	c.238G>A	p.Ala80Thr	missense_variant	4/9	ENST00000512528.3	NP_001350747.1
MTX3	NM_001167741.2 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	3/8		NP_001161213.1	Q5HYI7-5
MTX3	NM_001010891.5 linkuse as main transcript	c.238G>A	p.Ala80Thr	missense_variant	4/8		NP_001010891.4	Q5HYI7-4
MTX3	XM_017009440.2 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	3/7		XP_016864929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTX3	ENST00000512528.3 linkuse as main transcript	c.238G>A	p.Ala80Thr	missense_variant	4/9	1	NM_001363818.2	ENSP00000424798.2	Q5HYI7-1
MTX3	ENST00000509852.6 linkuse as main transcript	c.238G>A	p.Ala80Thr	missense_variant	4/8	1		ENSP00000423302.1	Q5HYI7-4
MTX3	ENST00000512560.5 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	3/8	2		ENSP00000423600.1	Q5HYI7-5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151932

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:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000462

AC:

AN:

216604

Hom.:

AF XY:

0.00

AC XY:

AN XY:

116854

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:

0.0000499

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1431540

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710968

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:

9.14e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74200

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:

0.0000948

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000831

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3476

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 08, 2023

The c.55G>A (p.A19T) 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 55, causing the alanine (A) at amino acid position 19 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

Uncertain

0.42

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

.;T;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.5

M;M;.;M

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.9

.;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.11

.;T;T;T

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.41, 0.98

.;B;.;D

Vest4

0.85

MutPred

0.55

Gain of phosphorylation at A80 (P = 0.0298);Gain of phosphorylation at A80 (P = 0.0298);.;Gain of phosphorylation at A80 (P = 0.0298);

MVP

0.59

MPC

0.17

ClinPred

0.90

GERP RS

5.4

Varity_R

0.36

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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