16-56639378-G-T

Position:

• chr16-56639378-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005946.3(MT1A):​c.94+49G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,586,494 control chromosomes in the GnomAD database, including 14,187 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: 34)
  • Exomes 𝑓: 0.13 (12846 hom.)
• Consequence: MT1A NM_005946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1A	NM_005946.3	c.94+49G>T		intron_variant		ENST00000290705.12	NP_005937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1A	ENST00000290705.12	c.94+49G>T		intron_variant		1	NM_005946.3	ENSP00000290705	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19838 AN: 152114 Hom.: 1337 Cov.: 34

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.144 AC: 36013 AN: 250018 Hom.: 2678 AF XY: 0.144 AC XY: 19435 AN XY: 135328

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.237

Gnomad SAS exome AF: 0.160

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.132 AC: 188951 AN: 1434262 Hom.: 12846 Cov.: 32 AF XY: 0.132 AC XY: 94673 AN XY: 714932

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.130 AC: 19855 AN: 152232 Hom.: 1341 Cov.: 34 AF XY: 0.133 AC XY: 9920 AN XY: 74426

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.137

Alfa AF: 0.129 Hom.: 2246

Bravo AF: 0.130

Asia WGS AF: 0.199 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.86

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: rs7190725; hg19: chr16-56673290; COSMIC: COSV51947984; COSMIC: COSV51947984;