Genetic Variant MTX1:c.772-12C>T (chr1-155212373-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002455.5(MTX1):c.772-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,613,036 control chromosomes in the GnomAD database, including 229,926 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 24916 hom., cov: 32)

Exomes 𝑓: 0.53 ( 205010 hom. )

Consequence

MTX1
NM_002455.5 intron

Scores

Splicing: ADA: 0.00001712

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

Publications

26 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:

GBA1LP (HGNC:):

GBA1LP links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTX1	NM_002455.5	MANE Select	c.772-12C>T		intron	N/A	NP_002446.3
	MTX1	NM_198883.3		c.679-12C>T		intron	N/A	NP_942584.2	Q13505-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTX1	ENST00000368376.8	TSL:1 MANE Select	c.772-12C>T	intron	N/A	ENSP00000357360.3	Q13505-1
MTX1	ENST00000316721.8	TSL:1	c.679-12C>T	intron	N/A	ENSP00000317106.4	Q13505-2
MTX1	ENST00000609421.1	TSL:1	c.325-12C>T	intron	N/A	ENSP00000476632.1	Q13505-3

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86296

AN:

151944

Hom.:

24877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.556

GnomAD2 exomes

AF:

0.565

AC:

141978

AN:

251214

AF XY:

0.553

show subpopulations

Gnomad AFR exome

AF:

0.654

Gnomad AMR exome

AF:

0.687

Gnomad ASJ exome

AF:

0.495

Gnomad EAS exome

AF:

0.780

Gnomad FIN exome

AF:

0.546

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.537

GnomAD4 exome

AF:

0.525

AC:

767367

AN:

1460974

Hom.:

205010

Cov.:

AF XY:

0.523

AC XY:

380045

AN XY:

726650

show subpopulations

African (AFR)

AF:

0.647

AC:

21641

AN:

33442

American (AMR)

AF:

0.682

AC:

30501

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

12852

AN:

26124

East Asian (EAS)

AF:

0.808

AC:

32045

AN:

39666

South Asian (SAS)

AF:

0.539

AC:

46446

AN:

86198

European-Finnish (FIN)

AF:

0.545

AC:

29098

AN:

53418

Middle Eastern (MID)

AF:

0.445

AC:

2564

AN:

5764

European-Non Finnish (NFE)

AF:

0.504

AC:

560137

AN:

1111310

Other (OTH)

AF:

0.532

AC:

32083

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

20833

41666

62500

83333

104166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16570

33140

49710

66280

82850

<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:

0.568

AC:

86381

AN:

152062

Hom.:

24916

Cov.:

AF XY:

0.570

AC XY:

42342

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.649

AC:

26933

AN:

41468

American (AMR)

AF:

0.616

AC:

9412

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.489

AC:

1696

AN:

3470

East Asian (EAS)

AF:

0.780

AC:

4033

AN:

5170

South Asian (SAS)

AF:

0.536

AC:

2581

AN:

4816

European-Finnish (FIN)

AF:

0.548

AC:

5799

AN:

10578

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.505

AC:

34295

AN:

67974

Other (OTH)

AF:

0.552

AC:

1165

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1923

3845

5768

7690

9613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.437

Hom.:

2077

Bravo

AF:

0.582

Asia WGS

AF:

0.664

AC:

2311

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.6

(source)

DANN

Benign

0.72

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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