16-56590167-A-G

Variant names:

• chr16-56590167-A-G
• rs11644094
• NM_005954.4:c.97+232A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MT3	NM_005954.4	c.97+232A>G		intron_variant	Intron 2 of 2	ENST00000200691.5	NP_005945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT3	ENST00000200691.5	c.97+232A>G		intron_variant	Intron 2 of 2	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

GnomAD2 exomes AF: 0.302 AC: 34223 AN: 113390 AF XY: 0.304

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 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

African (AFR) AF: 0.0861 AC: 1304 AN: 15148

American (AMR) AF: 0.265 AC: 8718 AN: 32838

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 5466 AN: 18306

East Asian (EAS) AF: 0.165 AC: 5208 AN: 31648

South Asian (SAS) AF: 0.239 AC: 14157 AN: 59168

European-Finnish (FIN) AF: 0.419 AC: 13519 AN: 32284

Middle Eastern (MID) AF: 0.300 AC: 1146 AN: 3816

European-Non Finnish (NFE) AF: 0.407 AC: 121756 AN: 299242

Other (OTH) AF: 0.342 AC: 9968 AN: 29158

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

African (AFR) AF: 0.0863 AC: 3582 AN: 41522

American (AMR) AF: 0.293 AC: 4471 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3468

East Asian (EAS) AF: 0.145 AC: 745 AN: 5150

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4814

European-Finnish (FIN) AF: 0.419 AC: 4431 AN: 10578

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27805 AN: 67920

Other (OTH) AF: 0.315 AC: 665 AN: 2108

Alfa AF: 0.334 Hom.: 9669

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
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11644094; hg19: chr16-56624079; COSMIC: COSV52365982;