chr16-56640239-C-T

Variant names:

• chr16-56640239-C-T
• rs904776
• NM_005946.3:c.*289C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005946.3(MT1A):​c.*289C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,088 control chromosomes in the GnomAD database, including 52,573 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 0.83 (52573 hom., cov: 31)
• Consequence: MT1A NM_005946.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 11 publications found

Genes affected

MT1A (HGNC:7393): (metallothionein 1A) 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. The conserved cysteine residues co-ordinate metal ions using mercaptide linkages. 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. Disruption of two metallothionein genes in mouse resulted in defects in protection against heavy metals, oxidative stress, immune reactions, carcinogens, and displayed obesity. [provided by RefSeq, Sep 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005946.3. 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
	MT1A	NM_005946.3	MANE Select	c.*289C>T		downstream_gene	N/A	NP_005937.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1A	ENST00000290705.12	TSL:1 MANE Select	c.*289C>T		downstream_gene	N/A	ENSP00000290705.8

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125513 AN: 151968 Hom.: 52554 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.898

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.848

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.826 AC: 125576 AN: 152088 Hom.: 52573 Cov.: 31 AF XY: 0.830 AC XY: 61732 AN XY: 74368

African (AFR) AF: 0.670 AC: 27766 AN: 41426

American (AMR) AF: 0.869 AC: 13278 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3221 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5138 AN: 5186

South Asian (SAS) AF: 0.887 AC: 4281 AN: 4824

European-Finnish (FIN) AF: 0.883 AC: 9351 AN: 10588

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59689 AN: 67998

Other (OTH) AF: 0.850 AC: 1791 AN: 2106

Alfa AF: 0.867 Hom.: 71141

Bravo AF: 0.820

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.67
DANN	Benign	0.50
PhyloP100		-1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs904776; hg19: chr16-56674151;