16-56632974-C-T

Variant names:

• chr16-56632974-C-T
• rs1827208
• NM_176870.3:c.28+215C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176870.3(MT1M):​c.28+215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,082 control chromosomes in the GnomAD database, including 23,910 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 0.54 (23910 hom., cov: 33)
• Consequence: MT1M NM_176870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176870.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1M	NM_176870.3	MANE Select	c.28+215C>T		intron	N/A	NP_789846.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1M	ENST00000379818.4	TSL:1 MANE Select	c.28+215C>T		intron	N/A	ENSP00000369146.3
	MT1M	ENST00000570233.1	TSL:3	c.28+215C>T		intron	N/A	ENSP00000457575.1
	MT1M	ENST00000858452.1		c.28+215C>T		intron	N/A	ENSP00000528511.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82661 AN: 151960 Hom.: 23904 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.566

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.544 AC: 82687 AN: 152082 Hom.: 23910 Cov.: 33 AF XY: 0.548 AC XY: 40715 AN XY: 74362

African (AFR) AF: 0.340 AC: 14088 AN: 41482

American (AMR) AF: 0.614 AC: 9388 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3470

East Asian (EAS) AF: 0.464 AC: 2395 AN: 5158

South Asian (SAS) AF: 0.506 AC: 2435 AN: 4816

European-Finnish (FIN) AF: 0.687 AC: 7273 AN: 10582

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43077 AN: 67972

Other (OTH) AF: 0.563 AC: 1188 AN: 2110

Alfa AF: 0.592 Hom.: 14804

Bravo AF: 0.532

Asia WGS AF: 0.510 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.42
PhyloP100		-0.30
PromoterAI		0.056	Neutral
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: rs1827208; hg19: chr16-56666886;