dbSNP rs768059574: MTX1:p.Thr120Lys (chr1-155209163-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002455.5(MTX1):c.359C>A(p.Thr120Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 1,500,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T120R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

MTX1
NM_002455.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

Variant links:

Genes affected

MTX1 (HGNC:7504): (metaxin 1) Predicted to be involved in mitochondrion organization. Part of MIB complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

MTX1 links:

THBS3 (HGNC:11787): (thrombospondin 3) The protein encoded by this gene belongs to the thrombospondin family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentameric molecule linked by a single disulfide bond. This gene shares a common promoter with metaxin 1. Alternate splicing results in coding and non-coding transcript variants. [provided by RefSeq, Nov 2011]

THBS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049195588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTX1	NM_002455.5 link	c.359C>A	p.Thr120Lys	missense_variant	Exon 1 of 8	ENST00000368376.8	NP_002446.3	Q13505-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTX1	ENST00000368376.8 link	c.359C>A	p.Thr120Lys	missense_variant	Exon 1 of 8	1	NM_002455.5	ENSP00000357360.3		Q13505-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000476

AC:

AN:

105072

Hom.:

AF XY:

0.0000173

AC XY:

AN XY:

57852

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:

0.000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000512

AC:

AN:

1348158

Hom.:

Cov.:

AF XY:

0.0000575

AC XY:

AN XY:

660886

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:

0.0000559

Gnomad4 OTH exome

AF:

0.000180

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000339

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.3

DANN

Benign

0.87

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.087

Sift

Benign

0.20

T;T

Sift4G

Uncertain

0.019

D;D

Polyphen

0.013

B;B

Vest4

0.086

MutPred

0.43

Gain of ubiquitination at T120 (P = 0.0094);Gain of ubiquitination at T120 (P = 0.0094);

MVP

0.19

MPC

0.31

ClinPred

0.062

GERP RS

-1.0

Varity_R

0.033

gMVP

0.19

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over