16-56590167-A-G

Position:

• chr16-56590167-A-G

Variant summary

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

The NM_005954.4(MT3):​c.97+232A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 673,654 control chromosomes in the GnomAD database, including 42,006 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 0.29 (7944 hom., cov: 31)
  • Exomes 𝑓: 0.35 (34062 hom.)
• Consequence: MT3 NM_005954.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825

Genes affected

MT3 (HGNC:7408): (metallothionein 3) 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. This gene family member displays tissue-specific expression, and contains a threonine insert near its N-terminus and a glutamate-rich hexapeptide insert near its C-terminus relative to the proteins encoded by other gene family members. It plays an important role in zinc and copper homeostasis, and is induced under hypoxic conditions. The encoded protein is a growth inhibitory factor, and reduced levels of the protein are observed in the brains of individuals with some metal-linked neurodegenerative disorders such as Alzheimer's disease. [provided by RefSeq, Sep 2017]

MT3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT3	NM_005954.4	c.97+232A>G		intron_variant		ENST00000200691.5	NP_005945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT3	ENST00000200691.5	c.97+232A>G		intron_variant		1	NM_005954.4	ENSP00000200691.5

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44261 AN: 151928 Hom.: 7949 Cov.: 31

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.319

GnomAD3 exomes AF: 0.302 AC: 34223 AN: 113390 Hom.: 5981 AF XY: 0.304 AC XY: 18621 AN XY: 61292

Gnomad AFR exome AF: 0.0717

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.240

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.347 AC: 181242 AN: 521608 Hom.: 34062 Cov.: 4 AF XY: 0.343 AC XY: 95659 AN XY: 278902

Gnomad4 AFR exome AF: 0.0861

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.291 AC: 44242 AN: 152046 Hom.: 7944 Cov.: 31 AF XY: 0.287 AC XY: 21335 AN XY: 74306

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.315

Alfa AF: 0.362 Hom.: 4382

Bravo AF: 0.272

Asia WGS AF: 0.216 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11644094; hg19: chr16-56624079; COSMIC: COSV52365982;