Variant 5-79989166-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000512528.3(MTX3):c.307C>T(p.Leu103Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000898 in 1,604,312 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000095 ( 1 hom. )

Consequence

MTX3
ENST00000512528.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10

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
MTX3	NM_001363818.2 linkuse as main transcript	c.307C>T	p.Leu103Phe	missense_variant	4/9	ENST00000512528.3	NP_001350747.1
MTX3	NM_001167741.2 linkuse as main transcript	c.124C>T	p.Leu42Phe	missense_variant	3/8		NP_001161213.1
MTX3	NM_001010891.5 linkuse as main transcript	c.307C>T	p.Leu103Phe	missense_variant	4/8		NP_001010891.4
MTX3	XM_017009440.2 linkuse as main transcript	c.124C>T	p.Leu42Phe	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.307C>T	p.Leu103Phe	missense_variant	4/9	1	NM_001363818.2	ENSP00000424798	P3	Q5HYI7-1
MTX3	ENST00000509852.6 linkuse as main transcript	c.307C>T	p.Leu103Phe	missense_variant	4/8	1		ENSP00000423302	A1	Q5HYI7-4
MTX3	ENST00000512560.5 linkuse as main transcript	c.124C>T	p.Leu42Phe	missense_variant	3/8	2		ENSP00000423600		Q5HYI7-5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000375

AC:

AN:

239940

Hom.:

AF XY:

0.0000385

AC XY:

AN XY:

129840

show subpopulations

Gnomad AFR exome

AF:

0.000206

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:

0.0000550

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000950

AC:

138

AN:

1452164

Hom.:

Cov.:

AF XY:

0.0000831

AC XY:

AN XY:

721838

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

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:

0.000120

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000776

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.000273

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

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

May 23, 2023

The c.124C>T (p.L42F) alteration is located in exon 3 (coding exon 2) of the MTX3 gene. This alteration results from a C to T substitution at nucleotide position 124, causing the leucine (L) at amino acid position 42 to be replaced by a phenylalanine (F). 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

0.47

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.76

T;D;D;T

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.5

M;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.5

.;D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.011

.;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D

Polyphen

1.0, 1.0

.;D;.;D

Vest4

0.83

MVP

0.77

MPC

0.24

ClinPred

0.78

GERP RS

5.5

Varity_R

0.49

gMVP

0.87

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