rs12448654

Positions:

• chr16-56667915-T-C

Variant summary

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

The NM_001301267.2(MT1G):​c.28+51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,606,400 control chromosomes in the GnomAD database, including 14,989 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 0.11 (1030 hom., cov: 33)
  • Exomes 𝑓: 0.14 (13959 hom.)
• Consequence: MT1G NM_001301267.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715

Genes affected

MT1G (HGNC:7399): (metallothionein 1G) Enables zinc ion binding activity. Involved in cellular response to metal ion; cellular response to vascular endothelial growth factor stimulus; and negative regulation of growth. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT1G (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1G	NM_001301267.2	c.28+51A>G		intron_variant		ENST00000379811.4	NP_001288196.1
MT1G	NM_005950.3	c.28+51A>G		intron_variant			NP_005941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1G	ENST00000379811.4	c.28+51A>G		intron_variant		1	NM_001301267.2	ENSP00000369139.4
MT1G	ENST00000444837.6	c.28+51A>G		intron_variant		1		ENSP00000391397.2
MT1G	ENST00000568675.1	n.56+51A>G		intron_variant		1
MT1G	ENST00000569500.5	c.28+51A>G		intron_variant		3		ENSP00000456675.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15973 AN: 152108 Hom.: 1030 Cov.: 33

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.123 AC: 30974 AN: 251382 Hom.: 2092 AF XY: 0.124 AC XY: 16861 AN XY: 135878

Gnomad AFR exome AF: 0.0337

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.0590

Gnomad EAS exome AF: 0.0674

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.135 AC: 197003 AN: 1454174 Hom.: 13959 Cov.: 30 AF XY: 0.135 AC XY: 97547 AN XY: 723890

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.0569

Gnomad4 EAS exome AF: 0.0788

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.105 AC: 15985 AN: 152226 Hom.: 1030 Cov.: 33 AF XY: 0.104 AC XY: 7752 AN XY: 74416

Gnomad4 AFR AF: 0.0375

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.0710

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.0993

Alfa AF: 0.107 Hom.: 254

Bravo AF: 0.0984

Asia WGS AF: 0.0810 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12448654; hg19: chr16-56701827; COSMIC: COSV60091328; COSMIC: COSV60091328;