Genetic Variant MT1X:c.29-95T>G (chr16-56683070-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005952.4(MT1X):c.29-95T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,456,520 control chromosomes in the GnomAD database, including 290,442 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 0.61 ( 29094 hom., cov: 33)

Exomes 𝑓: 0.63 ( 261348 hom. )

Consequence

MT1X
NM_005952.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

19 publications found

Variant links:

Genes affected

MT1X (HGNC:7405): (metallothionein 1X) Predicted to enable copper ion binding activity and zinc ion binding activity. Involved in cellular response to cadmium ion; cellular response to erythropoietin; and cellular response to zinc ion. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT1X links:

ENSG00000259827 (HGNC:):

ENSG00000259827 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1X	NM_005952.4 link	c.29-95T>G		intron_variant	Intron 1 of 2	ENST00000394485.5	NP_005943.1	P80297A0A140VJP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1X	ENST00000394485.5 link	c.29-95T>G		intron_variant	Intron 1 of 2	1	NM_005952.4	ENSP00000377995.4		P80297

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93379

AN:

151982

Hom.:

29068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.604

Gnomad EAS

AF:

0.916

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.663

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.621

Gnomad OTH

AF:

0.622

GnomAD4 exome

AF:

0.630

AC:

821709

AN:

1304420

Hom.:

261348

Cov.:

AF XY:

0.628

AC XY:

410670

AN XY:

654426

show subpopulations

African (AFR)

AF:

0.548

AC:

16530

AN:

30168

American (AMR)

AF:

0.696

AC:

30046

AN:

43152

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

14380

AN:

23820

East Asian (EAS)

AF:

0.904

AC:

34881

AN:

38590

South Asian (SAS)

AF:

0.577

AC:

46151

AN:

79946

European-Finnish (FIN)

AF:

0.664

AC:

34235

AN:

51538

Middle Eastern (MID)

AF:

0.574

AC:

2788

AN:

4856

European-Non Finnish (NFE)

AF:

0.622

AC:

608258

AN:

977570

Other (OTH)

AF:

0.629

AC:

34440

AN:

54780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

14255

28510

42765

57020

71275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15812

31624

47436

63248

79060

<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:

0.614

AC:

93451

AN:

152100

Hom.:

29094

Cov.:

AF XY:

0.616

AC XY:

45825

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.550

AC:

22812

AN:

41480

American (AMR)

AF:

0.640

AC:

9794

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

2095

AN:

3468

East Asian (EAS)

AF:

0.915

AC:

4736

AN:

5174

South Asian (SAS)

AF:

0.596

AC:

2877

AN:

4826

European-Finnish (FIN)

AF:

0.663

AC:

7011

AN:

10574

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.621

AC:

42196

AN:

67968

Other (OTH)

AF:

0.627

AC:

1322

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1888

3777

5665

7554

9442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.619

Hom.:

112150

Bravo

AF:

0.613

Asia WGS

AF:

0.752

AC:

2613

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.52

(source)

DANN

Benign

0.47

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over