dbSNP rs10636: MT2A:c.*77G>C (chr16-56609431-G-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_005953.5(MT2A):c.*77G>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 0.265 in 1,514,694 control chromosomes in the GnomAD database, including 54,806 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 0.26 ( 5344 hom., cov: 33)

Exomes 𝑓: 0.27 ( 49462 hom. )

Consequence

MT2A
NM_005953.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.932

Publications

71 publications found

Variant links:

Genes affected

MT2A (HGNC:7406): (metallothionein 2A) This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions, altering the intracellular concentration of heavy metals in the cell. These proteins act as anti-oxidants, protect against hydroxyl free radicals, are important in homeostatic control of metal in the cell, and play a role in detoxification of heavy metals. The encoded protein interacts with the protein encoded by the homeobox containing 1 gene in some cell types, controlling intracellular zinc levels, affecting apoptotic and autophagy pathways. Some polymorphisms in this gene are associated with an increased risk of cancer. [provided by RefSeq, Sep 2017]

MT2A links:

ENSG00000260823 (HGNC:):

ENSG00000260823 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=-0.79).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT2A	NM_005953.5 link	c.*77G>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000245185.6	NP_005944.1	P02795

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT2A	ENST00000245185.6 link	c.*77G>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_005953.5	ENSP00000245185.5		P02795

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39988

AN:

152024

Hom.:

5336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.250

GnomAD4 exome

AF:

0.266

AC:

361996

AN:

1362554

Hom.:

49462

Cov.:

AF XY:

0.269

AC XY:

181932

AN XY:

675094

show subpopulations

African (AFR)

AF:

0.249

AC:

7523

AN:

30248

American (AMR)

AF:

0.231

AC:

7140

AN:

30890

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

6251

AN:

21670

East Asian (EAS)

AF:

0.236

AC:

9121

AN:

38682

South Asian (SAS)

AF:

0.403

AC:

30388

AN:

75334

European-Finnish (FIN)

AF:

0.236

AC:

12012

AN:

50986

Middle Eastern (MID)

AF:

0.227

AC:

1156

AN:

5096

European-Non Finnish (NFE)

AF:

0.260

AC:

273578

AN:

1053214

Other (OTH)

AF:

0.263

AC:

14827

AN:

56434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

11242

22483

33725

44966

56208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9434

18868

28302

37736

47170

<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:

0.263

AC:

40003

AN:

152140

Hom.:

5344

Cov.:

AF XY:

0.262

AC XY:

19492

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.254

AC:

10541

AN:

41480

American (AMR)

AF:

0.242

AC:

3699

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1033

AN:

3472

East Asian (EAS)

AF:

0.259

AC:

1338

AN:

5174

South Asian (SAS)

AF:

0.393

AC:

1899

AN:

4828

European-Finnish (FIN)

AF:

0.238

AC:

2519

AN:

10590

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18088

AN:

67992

Other (OTH)

AF:

0.248

AC:

522

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1436

2872

4307

5743

7179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.265

Hom.:

676

Bravo

AF:

0.259

Asia WGS

AF:

0.299

AC:

1043

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.7

(source)

DANN

Benign

0.36

PhyloP100

-0.93

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

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