rs10636

Positions:

• chr16-56609431-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MT2A	NM_005953.5	c.*77G>C		3_prime_UTR_variant	3/3	ENST00000245185.6	NP_005944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT2A	ENST00000245185.6	c.*77G>C		3_prime_UTR_variant	3/3	1	NM_005953.5	ENSP00000245185.5

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39988 AN: 152024 Hom.: 5336 Cov.: 33

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.: 24 AF XY: 0.269 AC XY: 181932 AN XY: 675094

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.263 AC: 40003 AN: 152140 Hom.: 5344 Cov.: 33 AF XY: 0.262 AC XY: 19492 AN XY: 74404

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.248

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
DANN	Benign	0.36
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

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

LitVar

Other links and lift over

dbSNP: rs10636; hg19: chr16-56643343; COSMIC: COSV55330113; COSMIC: COSV55330113;