dbSNP rs9936741: MT1M:c.*31T>C (chr16-56633873-T-C) – 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.*31T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,610,172 control chromosomes in the GnomAD database, including 1,491 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 0.060 ( 536 hom., cov: 33)

Exomes 𝑓: 0.026 ( 955 hom. )

Consequence

MT1M
NM_176870.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

21 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1M	NM_176870.3 link	c.*31T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000379818.4	NP_789846.2	Q8N339A0A024R6T4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1M	ENST00000379818.4 link	c.*31T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_176870.3	ENSP00000369146.3		Q8N339

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9051

AN:

152184

Hom.:

534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0383

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.0963

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0195

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0488

GnomAD2 exomes

AF:

0.0378

AC:

9467

AN:

250176

AF XY:

0.0341

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.00762

Gnomad EAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0221

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0264

AC:

38436

AN:

1457870

Hom.:

955

Cov.:

AF XY:

0.0256

AC XY:

18562

AN XY:

725064

show subpopulations

African (AFR)

AF:

0.154

AC:

5155

AN:

33388

American (AMR)

AF:

0.0438

AC:

1948

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.00787

AC:

205

AN:

26038

East Asian (EAS)

AF:

0.0741

AC:

2937

AN:

39638

South Asian (SAS)

AF:

0.0228

AC:

1961

AN:

86096

European-Finnish (FIN)

AF:

0.0229

AC:

1219

AN:

53326

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0206

AC:

22880

AN:

1108928

Other (OTH)

AF:

0.0343

AC:

2064

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2056

4113

6169

8226

10282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1008

2016

3024

4032

5040

<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:

0.0595

AC:

9069

AN:

152302

Hom.:

536

Cov.:

AF XY:

0.0578

AC XY:

4303

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.149

AC:

6181

AN:

41550

American (AMR)

AF:

0.0383

AC:

586

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.0959

AC:

497

AN:

5182

South Asian (SAS)

AF:

0.0255

AC:

123

AN:

4826

European-Finnish (FIN)

AF:

0.0195

AC:

207

AN:

10628

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0196

AC:

1332

AN:

68018

Other (OTH)

AF:

0.0492

AC:

104

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

422

843

1265

1686

2108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0324

Hom.:

276

Bravo

AF:

0.0666

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.30

(source)

DANN

Benign

0.43

PhyloP100

-1.5

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