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:

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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=-0.88).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176870.3. 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
	MT1M	NM_176870.3	MANE Select	c.95-49C>T		intron	N/A	NP_789846.2	Q8N339

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MT1M	ENST00000379818.4	TSL:1 MANE Select	c.95-49C>T	intron	N/A	ENSP00000369146.3	Q8N339
MT1M	ENST00000858452.1		c.29-49C>T	intron	N/A	ENSP00000528511.1
MT1M	ENST00000570233.1	TSL:3	c.*184C>T	downstream_gene	N/A	ENSP00000457575.1	H3BUC6

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over