Genetic Variant MT1M:c.95-49C>T (chr16-56633702-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_176870.3(MT1M):c.95-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,609,584 control chromosomes in the GnomAD database, including 128,362 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 0.35 ( 10207 hom., cov: 33)

Exomes 𝑓: 0.40 ( 118155 hom. )

Consequence

MT1M
NM_176870.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

Publications

30 publications found

Variant links:

Genes affected

MT1M (HGNC:14296): (metallothionein 1M) This gene encodes a member of the metallothionein superfamily, type 1 family. Metallothioneins have a high content of cysteine residues that bind various heavy metals. These genes are transcriptionally regulated by both heavy metals and glucocorticoids. [provided by RefSeq, Oct 2011]

MT1M links:

Genome browser will be placed here

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=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1M	NM_176870.3 link	c.95-49C>T		intron_variant	Intron 2 of 2	ENST00000379818.4	NP_789846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1M	ENST00000379818.4 link	c.95-49C>T		intron_variant	Intron 2 of 2	1	NM_176870.3	ENSP00000369146.3
MT1M	ENST00000570233.1 link	c.*184C>T		downstream_gene_variant		3		ENSP00000457575.1

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53411

AN:

151918

Hom.:

10197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.382

GnomAD2 exomes

AF:

0.398

AC:

100064

AN:

251130

AF XY:

0.401

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.246

Gnomad FIN exome

AF:

0.424

Gnomad NFE exome

AF:

0.408

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.400

AC:

582584

AN:

1457548

Hom.:

118155

Cov.:

AF XY:

0.401

AC XY:

290972

AN XY:

725430

show subpopulations

African (AFR)

AF:

0.190

AC:

6346

AN:

33400

American (AMR)

AF:

0.484

AC:

21630

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

11464

AN:

26110

East Asian (EAS)

AF:

0.298

AC:

11844

AN:

39680

South Asian (SAS)

AF:

0.415

AC:

35755

AN:

86158

European-Finnish (FIN)

AF:

0.428

AC:

22793

AN:

53270

Middle Eastern (MID)

AF:

0.461

AC:

2621

AN:

5688

European-Non Finnish (NFE)

AF:

0.403

AC:

446532

AN:

1108294

Other (OTH)

AF:

0.392

AC:

23599

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

21130

42261

63391

84522

105652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13722

27444

41166

54888

68610

<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:

0.351

AC:

53438

AN:

152036

Hom.:

10207

Cov.:

AF XY:

0.358

AC XY:

26610

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.198

AC:

8207

AN:

41486

American (AMR)

AF:

0.456

AC:

6968

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

1495

AN:

3472

East Asian (EAS)

AF:

0.255

AC:

1318

AN:

5164

South Asian (SAS)

AF:

0.410

AC:

1974

AN:

4814

European-Finnish (FIN)

AF:

0.434

AC:

4579

AN:

10560

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.406

AC:

27581

AN:

67940

Other (OTH)

AF:

0.382

AC:

808

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1702

3403

5105

6806

8508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.347

Hom.:

2389

Bravo

AF:

0.347

Asia WGS

AF:

0.363

AC:

1263

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.50

(source)

DANN

Benign

0.97

PhyloP100

-1.7

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