16-56638488-G-A

Variant names:

• chr16-56638488-G-A
• rs9922409
• NM_005946.3:c.-251G>A

Variant summary

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

The NM_005946.3(MT1A):​c.-251G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,244 control chromosomes in the GnomAD database, including 844 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 0.10 (844 hom., cov: 32)
• Consequence: MT1A NM_005946.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1A	NM_005946.3	c.-251G>A		upstream_gene_variant		ENST00000290705.12	NP_005937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1A	ENST00000290705.12	c.-251G>A		upstream_gene_variant		1	NM_005946.3	ENSP00000290705.8

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15347 AN: 152126 Hom.: 839 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.101 AC: 15367 AN: 152244 Hom.: 844 Cov.: 32 AF XY: 0.104 AC XY: 7738 AN XY: 74452

African (AFR) AF: 0.0584 AC: 2427 AN: 41572

American (AMR) AF: 0.123 AC: 1887 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 595 AN: 3466

East Asian (EAS) AF: 0.230 AC: 1182 AN: 5150

South Asian (SAS) AF: 0.161 AC: 779 AN: 4830

European-Finnish (FIN) AF: 0.104 AC: 1106 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6977 AN: 68000

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.0405 Hom.: 29

Bravo AF: 0.101

Asia WGS AF: 0.183 AC: 633 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.84
PhyloP100		-0.12
PromoterAI		0.042	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9922409; hg19: chr16-56672400;