rs35346959

Variant names:

• chr16-56637955-A-G
• rs35346959
• ENST00000908024.1:c.-376A>G

Variant summary

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

The ENST00000908024.1(MT1A):​c.-376A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,222 control chromosomes in the GnomAD database, including 1,341 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 0.13 (1341 hom., cov: 33)
• Consequence: MT1A ENST00000908024.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908024.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1A	ENST00000908024.1		c.-376A>G		upstream_gene	N/A	ENSP00000578083.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19874 AN: 152104 Hom.: 1337 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.131 AC: 19892 AN: 152222 Hom.: 1341 Cov.: 33 AF XY: 0.134 AC XY: 9944 AN XY: 74424

African (AFR) AF: 0.116 AC: 4806 AN: 41520

American (AMR) AF: 0.138 AC: 2109 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1202 AN: 5172

South Asian (SAS) AF: 0.176 AC: 848 AN: 4820

European-Finnish (FIN) AF: 0.127 AC: 1348 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8378 AN: 68010

Other (OTH) AF: 0.138 AC: 291 AN: 2114

Alfa AF: 0.124 Hom.: 144

Bravo AF: 0.130

Asia WGS AF: 0.196 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.3
DANN	Benign	0.68
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs35346959; hg19: chr16-56671867;