16-56639236-A-G

Variant names:

• chr16-56639236-A-G
• rs11076161
• NM_005946.3:c.29-28A>G

Variant summary

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

The NM_005946.3(MT1A):​c.29-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,608,540 control chromosomes in the GnomAD database, including 418,039 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 0.67 (34550 hom., cov: 34)
  • Exomes 𝑓: 0.72 (383489 hom.)
• Consequence: MT1A NM_005946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 33 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1A	NM_005946.3	MANE Select	c.29-28A>G		intron	N/A	NP_005937.2	P04731

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1A	ENST00000290705.12	TSL:1 MANE Select	c.29-28A>G		intron	N/A	ENSP00000290705.8	P04731
	MT1A	ENST00000908024.1		c.29-28A>G		intron	N/A	ENSP00000578083.1
	MT1A	ENST00000927706.1		c.29-67A>G		intron	N/A	ENSP00000597765.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101508 AN: 151772 Hom.: 34545 Cov.: 34

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.688

GnomAD2 exomes AF: 0.707 AC: 177397 AN: 250804 AF XY: 0.712

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.686

Gnomad ASJ exome AF: 0.737

Gnomad EAS exome AF: 0.655

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.740

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.724 AC: 1055031 AN: 1456650 Hom.: 383489 Cov.: 42 AF XY: 0.725 AC XY: 525176 AN XY: 724750

African (AFR) AF: 0.519 AC: 17325 AN: 33392

American (AMR) AF: 0.691 AC: 30736 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 19018 AN: 25940

East Asian (EAS) AF: 0.705 AC: 27922 AN: 39584

South Asian (SAS) AF: 0.700 AC: 60320 AN: 86170

European-Finnish (FIN) AF: 0.734 AC: 38920 AN: 52998

Middle Eastern (MID) AF: 0.788 AC: 4291 AN: 5446

European-Non Finnish (NFE) AF: 0.734 AC: 813900 AN: 1108640

Other (OTH) AF: 0.710 AC: 42599 AN: 59988

GnomAD4 genome AF: 0.668 AC: 101535 AN: 151890 Hom.: 34550 Cov.: 34 AF XY: 0.671 AC XY: 49779 AN XY: 74240

African (AFR) AF: 0.521 AC: 21546 AN: 41384

American (AMR) AF: 0.706 AC: 10789 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2555 AN: 3468

East Asian (EAS) AF: 0.661 AC: 3411 AN: 5162

South Asian (SAS) AF: 0.686 AC: 3311 AN: 4830

European-Finnish (FIN) AF: 0.735 AC: 7758 AN: 10552

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.736 AC: 49941 AN: 67890

Other (OTH) AF: 0.685 AC: 1449 AN: 2116

Alfa AF: 0.686 Hom.: 5074

Bravo AF: 0.663

Asia WGS AF: 0.669 AC: 2327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.72
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11076161; hg19: chr16-56673148; COSMIC: COSV51947364; COSMIC: COSV51947364;