rs1827210

Positions:

• chr16-56633370-C-A
• chr16-56633370-C-G
• chr16-56633370-C-T

Variant summary

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

The NM_176870.3(MT1M):​c.59C>A​(p.Thr20Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,614,012 control chromosomes in the GnomAD database, including 562,517 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.77 (45971 hom., cov: 34)
  • Exomes 𝑓: 0.84 (516546 hom.)
• Consequence: MT1M NM_176870.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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 (MetaRNN=9.826878E-7).
• 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	Protein	UniProt
MT1M	NM_176870.3	c.59C>A	p.Thr20Lys	missense_variant	2/3	ENST00000379818.4	NP_789846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1M	ENST00000379818.4	c.59C>A	p.Thr20Lys	missense_variant	2/3	1	NM_176870.3	ENSP00000369146	P1
MT1M	ENST00000570233.1	c.59C>A	p.Thr20Lys	missense_variant	2/2	3		ENSP00000457575

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116959 AN: 152044 Hom.: 45962 Cov.: 34

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.788

GnomAD3 exomes AF: 0.808 AC: 202987 AN: 251280 Hom.: 82782 AF XY: 0.815 AC XY: 110734 AN XY: 135880

Gnomad AFR exome AF: 0.590

Gnomad AMR exome AF: 0.784

Gnomad ASJ exome AF: 0.803

Gnomad EAS exome AF: 0.661

Gnomad SAS exome AF: 0.818

Gnomad FIN exome AF: 0.860

Gnomad NFE exome AF: 0.856

Gnomad OTH exome AF: 0.831

GnomAD4 exome AF: 0.839 AC: 1226355 AN: 1461850 Hom.: 516546 Cov.: 117 AF XY: 0.839 AC XY: 610393 AN XY: 727232

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.790

Gnomad4 ASJ exome AF: 0.798

Gnomad4 EAS exome AF: 0.708

Gnomad4 SAS exome AF: 0.814

Gnomad4 FIN exome AF: 0.857

Gnomad4 NFE exome AF: 0.856

Gnomad4 OTH exome AF: 0.813

GnomAD4 genome AF: 0.769 AC: 117003 AN: 152162 Hom.: 45971 Cov.: 34 AF XY: 0.769 AC XY: 57178 AN XY: 74380

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.783

Alfa AF: 0.811 Hom.: 18324

Bravo AF: 0.758

ESP6500AA AF: 0.602 AC: 2646

ESP6500EA AF: 0.851 AC: 7317

ExAC AF: 0.806 AC: 97904

Asia WGS AF: 0.732 AC: 2548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.50
DANN	Benign	0.77
DEOGEN2	Benign	0.071	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.029	T;T
MetaRNN	Benign	9.8e-7	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	4.0	N;N
REVEL	Benign	0.019
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.061
MPC		0.012
ClinPred		0.00022	T
GERP RS		-0.081
Varity_R		0.047
gMVP		0.033

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: rs1827210; hg19: chr16-56667282; COSMIC: COSV65835940; COSMIC: COSV65835940;