16-56640199-C-T

Variant names:

• chr16-56640199-C-T
• rs904777
• NM_005946.3:c.*249C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005946.3(MT1A):​c.*249C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MT1A NM_005946.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1A	NM_005946.3	c.*249C>T		downstream_gene_variant		ENST00000290705.12	NP_005937.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1A	ENST00000290705.12	c.*249C>T		downstream_gene_variant		1	NM_005946.3	ENSP00000290705.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000358 AC: 1 AN: 279006 Hom.: 0 AF XY: 0.00000690 AC XY: 1 AN XY: 144980

African (AFR) AF: 0.00 AC: 0 AN: 8312

American (AMR) AF: 0.00 AC: 0 AN: 10896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7968

East Asian (EAS) AF: 0.00 AC: 0 AN: 16052

South Asian (SAS) AF: 0.00 AC: 0 AN: 24116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1570

European-Non Finnish (NFE) AF: 0.00000550 AC: 1 AN: 181876

Other (OTH) AF: 0.00 AC: 0 AN: 15726

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.43
PhyloP100		0.032

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: rs904777; hg19: chr16-56674111;