rs10636

Variant names:

• chr16-56609431-G-C
• rs10636
• NM_005953.5:c.*77G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-56609431-G-C
• chr16-56609431-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 71 publications found

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]

ENSG00000260823 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005953.5. 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
	MT2A	NM_005953.5	MANE Select	c.*77G>C		3_prime_UTR	Exon 3 of 3	NP_005944.1	P02795

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT2A	ENST00000245185.6	TSL:1 MANE Select	c.*77G>C		3_prime_UTR	Exon 3 of 3	ENSP00000245185.5	P02795
	MT2A	ENST00000561491.1	TSL:2	c.*246G>C		3_prime_UTR	Exon 2 of 2	ENSP00000456804.1	H3BSP9
	MT2A	ENST00000931885.1		c.*77G>C		3_prime_UTR	Exon 3 of 3	ENSP00000601944.1

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

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

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

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: 73 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18088 AN: 67992

Other (OTH) AF: 0.248 AC: 522 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
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)

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

Other links and lift over

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