16-56639236-A-G

Position:

• chr16-56639236-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1A	NM_005946.3	c.29-28A>G		intron_variant		ENST00000290705.12	NP_005937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1A	ENST00000290705.12	c.29-28A>G		intron_variant		1	NM_005946.3	ENSP00000290705.8

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

GnomAD3 exomes AF: 0.707 AC: 177397 AN: 250804 Hom.: 63243 AF XY: 0.712 AC XY: 96550 AN XY: 135614

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 SAS exome AF: 0.705

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

Gnomad4 AFR exome AF: 0.519

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.733

Gnomad4 EAS exome AF: 0.705

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.734

Gnomad4 NFE exome AF: 0.734

Gnomad4 OTH exome AF: 0.710

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

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.685

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs11076161; hg19: chr16-56673148; COSMIC: COSV51947364; COSMIC: COSV51947364;