rs527512238

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002455.5(MTX1):c.350T>C(p.Leu117Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,515,770 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

MTX1
NM_002455.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.16

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

THBS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014091641).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002455.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTX1	NM_002455.5	MANE Select	c.350T>C	p.Leu117Pro	missense	Exon 1 of 8	NP_002446.3
MTX1	NM_198883.3		c.350T>C	p.Leu117Pro	missense	Exon 1 of 7	NP_942584.2	Q13505-2
THBS3	NM_001407556.1		c.-284A>G		5_prime_UTR	Exon 1 of 23	NP_001394485.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTX1	ENST00000368376.8	TSL:1 MANE Select	c.350T>C	p.Leu117Pro	missense	Exon 1 of 8	ENSP00000357360.3	Q13505-1
MTX1	ENST00000316721.8	TSL:1	c.350T>C	p.Leu117Pro	missense	Exon 1 of 7	ENSP00000317106.4	Q13505-2
MTX1	ENST00000609421.1	TSL:1	c.-98T>C		upstream_gene	N/A	ENSP00000476632.1	Q13505-3

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000168

AC:

AN:

119070

AF XY:

0.000214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000516

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000873

GnomAD4 exome

AF:

0.000185

AC:

252

AN:

1363496

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

126

AN XY:

669230

show subpopulations

African (AFR)

AF:

0.000435

AC:

AN:

29882

American (AMR)

AF:

0.000620

AC:

AN:

30652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23560

East Asian (EAS)

AF:

0.00

AC:

AN:

34858

South Asian (SAS)

AF:

0.00

AC:

AN:

76398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46696

Middle Eastern (MID)

AF:

0.00171

AC:

AN:

4690

European-Non Finnish (NFE)

AF:

0.000175

AC:

186

AN:

1060548

Other (OTH)

AF:

0.000463

AC:

AN:

56212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41538

American (AMR)

AF:

0.000523

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000230

ExAC

AF:

0.0000869

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.038

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.018

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.30

M_CAP

Benign

0.016

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

PhyloP100

-4.2

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.090

REVEL

Benign

0.019

Sift

Benign

0.11

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.036

MutPred

0.36

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.076

MPC

0.38

ClinPred

0.11

GERP RS

-8.4

PromoterAI

-0.084

Neutral

(source)

Varity_R

0.066

gMVP

0.075

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over