Variant 5-79989216-G-C 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.257C>G(p.Ala86Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,605,814 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. A86T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MTX3
ENST00000512528.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.15

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=0.4176613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTX3	NM_001363818.2 linkuse as main transcript	c.257C>G	p.Ala86Gly	missense_variant	4/9	ENST00000512528.3	NP_001350747.1
MTX3	NM_001167741.2 linkuse as main transcript	c.74C>G	p.Ala25Gly	missense_variant	3/8		NP_001161213.1
MTX3	NM_001010891.5 linkuse as main transcript	c.257C>G	p.Ala86Gly	missense_variant	4/8		NP_001010891.4
MTX3	XM_017009440.2 linkuse as main transcript	c.74C>G	p.Ala25Gly	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.257C>G	p.Ala86Gly	missense_variant	4/9	1	NM_001363818.2	ENSP00000424798	P3	Q5HYI7-1
MTX3	ENST00000509852.6 linkuse as main transcript	c.257C>G	p.Ala86Gly	missense_variant	4/8	1		ENSP00000423302	A1	Q5HYI7-4
MTX3	ENST00000512560.5 linkuse as main transcript	c.74C>G	p.Ala25Gly	missense_variant	3/8	2		ENSP00000423600		Q5HYI7-5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151968

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:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000377

AC:

AN:

238650

Hom.:

AF XY:

0.0000465

AC XY:

AN XY:

129130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000247

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000925

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000289

AC:

AN:

1453846

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

722574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000454

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000344

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000998

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74204

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:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.0000497

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

Jun 30, 2022

The c.74C>G (p.A25G) alteration is located in exon 3 (coding exon 2) of the MTX3 gene. This alteration results from a C to G substitution at nucleotide position 74, causing the alanine (A) at amino acid position 25 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

Benign

0.31

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

.;T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;T;D;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.42

T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.9

M;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.9

.;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.046

.;D;T;T

Sift4G

Benign

0.091

T;D;D;T

Polyphen

0.61, 1.0

.;P;.;D

Vest4

0.60

MVP

0.55

MPC

0.059

ClinPred

0.75

GERP RS

5.4

Varity_R

0.53

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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