rs2270837

chr16-56633942-A-G

Variant summary

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

The NM_176870.3(MT1M):c.*100A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,253,278 control chromosomes in the GnomAD database, including 436,169 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 0.77 (45872 hom., cov: 33)
  • Exomes 𝑓: 0.84 (390297 hom.)
• Consequence: MT1M NM_176870.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

MT1M (HGNC:14296): (metallothionein 1M) This gene encodes a member of the metallothionein superfamily, type 1 family. Metallothioneins have a high content of cysteine residues that bind various heavy metals. These genes are transcriptionally regulated by both heavy metals and glucocorticoids. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT1M	NM_176870.3	c.*100A>G		3_prime_UTR_variant	3/3	ENST00000379818.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT1M	ENST00000379818.4	c.*100A>G		3_prime_UTR_variant	3/3	1	NM_176870.3	P1

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116810 AN: 152104 Hom.: 45863 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.840 AC: 924779 AN: 1101056 Hom.: 390297 Cov.: 14 AF XY: 0.840 AC XY: 465617 AN XY: 554282

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.799

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.817

Gnomad4 FIN exome AF: 0.860

Gnomad4 NFE exome AF: 0.858

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.768 AC: 116854 AN: 152222 Hom.: 45872 Cov.: 33 AF XY: 0.767 AC XY: 57109 AN XY: 74416

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.854

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.783

Alfa AF: 0.809 Hom.: 6309

Bravo AF: 0.756

Asia WGS AF: 0.732 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.6
Dann	Benign	0.68

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: rs2270837; hg19: chr16-56667854; COSMIC: COSV51947239; COSMIC: COSV51947239;