rs9936741

Positions:

• chr16-56633873-T-C

Variant summary

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

The NM_176870.3(MT1M):​c.*31T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,610,172 control chromosomes in the GnomAD database, including 1,491 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 0.060 (536 hom., cov: 33)
  • Exomes 𝑓: 0.026 (955 hom.)
• Consequence: MT1M NM_176870.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1M	NM_176870.3	c.*31T>C		3_prime_UTR_variant	3/3	ENST00000379818.4	NP_789846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1M	ENST00000379818.4	c.*31T>C		3_prime_UTR_variant	3/3	1	NM_176870.3	ENSP00000369146.3

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9051 AN: 152184 Hom.: 534 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0488

GnomAD3 exomes AF: 0.0378 AC: 9467 AN: 250176 Hom.: 366 AF XY: 0.0341 AC XY: 4607 AN XY: 135278

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.0466

Gnomad ASJ exome AF: 0.00762

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.0213

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.0190

Gnomad OTH exome AF: 0.0288

GnomAD4 exome AF: 0.0264 AC: 38436 AN: 1457870 Hom.: 955 Cov.: 33 AF XY: 0.0256 AC XY: 18562 AN XY: 725064

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0438

Gnomad4 ASJ exome AF: 0.00787

Gnomad4 EAS exome AF: 0.0741

Gnomad4 SAS exome AF: 0.0228

Gnomad4 FIN exome AF: 0.0229

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0343

GnomAD4 genome AF: 0.0595 AC: 9069 AN: 152302 Hom.: 536 Cov.: 33 AF XY: 0.0578 AC XY: 4303 AN XY: 74478

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0195

Gnomad4 NFE AF: 0.0196

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0272 Hom.: 143

Bravo AF: 0.0666

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30
DANN	Benign	0.43

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: rs9936741; hg19: chr16-56667785; COSMIC: COSV51947785; COSMIC: COSV51947785;