dbSNP rs2270837: MT1M:c.*100A>G (chr16-56633942-A-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_176870.3(MT1M):c.*100A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,253,278 control chromosomes in the GnomAD database, including 436,169 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 0.77 ( 45872 hom., cov: 33)

Exomes 𝑓: 0.84 ( 390297 hom. )

Consequence

MT1M
NM_176870.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.259

Publications

20 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1M	NM_176870.3	MANE Select	c.*100A>G		3_prime_UTR	Exon 3 of 3	NP_789846.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1M	ENST00000379818.4	TSL:1 MANE Select	c.*100A>G		3_prime_UTR	Exon 3 of 3	ENSP00000369146.3
	MT1M	ENST00000858452.1		c.*100A>G		3_prime_UTR	Exon 2 of 2	ENSP00000528511.1

Frequencies

GnomAD3 genomes

AF:

0.768

AC:

116810

AN:

152104

Hom.:

45863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.591

Gnomad AMI

AF:

0.730

Gnomad AMR

AF:

0.807

Gnomad ASJ

AF:

0.808

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.795

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.839

Gnomad NFE

AF:

0.857

Gnomad OTH

AF:

0.788

GnomAD4 exome

AF:

0.840

AC:

924779

AN:

1101056

Hom.:

390297

Cov.:

AF XY:

0.840

AC XY:

465617

AN XY:

554282

show subpopulations

African (AFR)

AF:

0.590

AC:

14926

AN:

25316

American (AMR)

AF:

0.802

AC:

26547

AN:

33090

Ashkenazi Jewish (ASJ)

AF:

0.799

AC:

16125

AN:

20186

East Asian (EAS)

AF:

0.711

AC:

26691

AN:

37556

South Asian (SAS)

AF:

0.817

AC:

56359

AN:

69002

European-Finnish (FIN)

AF:

0.860

AC:

40068

AN:

46616

Middle Eastern (MID)

AF:

0.867

AC:

4256

AN:

4910

European-Non Finnish (NFE)

AF:

0.858

AC:

700840

AN:

816584

Other (OTH)

AF:

0.815

AC:

38967

AN:

47796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

7080

14160

21240

28320

35400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14244

28488

42732

56976

71220

<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:

0.768

AC:

116854

AN:

152222

Hom.:

45872

Cov.:

AF XY:

0.767

AC XY:

57109

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.590

AC:

24486

AN:

41494

American (AMR)

AF:

0.807

AC:

12349

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

2804

AN:

3472

East Asian (EAS)

AF:

0.670

AC:

3468

AN:

5176

South Asian (SAS)

AF:

0.797

AC:

3845

AN:

4824

European-Finnish (FIN)

AF:

0.854

AC:

9064

AN:

10614

Middle Eastern (MID)

AF:

0.847

AC:

249

AN:

294

European-Non Finnish (NFE)

AF:

0.857

AC:

58268

AN:

68024

Other (OTH)

AF:

0.783

AC:

1655

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1333

2667

4000

5334

6667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.802

Hom.:

6459

Bravo

AF:

0.756

Asia WGS

AF:

0.732

AC:

2549

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.6

(source)

DANN

Benign

0.68

PhyloP100

-0.26

Mutation Taster

=95/5

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