rs12448654

Variant names:

• chr16-56667915-T-C
• rs12448654
• NM_001301267.2:c.28+51A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MT1G	NM_001301267.2	c.28+51A>G		intron_variant	Intron 1 of 2	ENST00000379811.4	NP_001288196.1
MT1G	NM_005950.3	c.28+51A>G		intron_variant	Intron 1 of 2		NP_005941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1G	ENST00000379811.4	c.28+51A>G		intron_variant	Intron 1 of 2	1	NM_001301267.2	ENSP00000369139.4
MT1G	ENST00000444837.6	c.28+51A>G		intron_variant	Intron 1 of 2	1		ENSP00000391397.2
MT1G	ENST00000568675.1	n.56+51A>G		intron_variant	Intron 1 of 1	1
MT1G	ENST00000569500.5	c.28+51A>G		intron_variant	Intron 1 of 1	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

GnomAD2 exomes AF: 0.123 AC: 30974 AN: 251382 AF XY: 0.124

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 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

African (AFR) AF: 0.0313 AC: 1042 AN: 33318

American (AMR) AF: 0.145 AC: 6471 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0569 AC: 1484 AN: 26064

East Asian (EAS) AF: 0.0788 AC: 3121 AN: 39598

South Asian (SAS) AF: 0.115 AC: 9868 AN: 86090

European-Finnish (FIN) AF: 0.152 AC: 8084 AN: 53226

Middle Eastern (MID) AF: 0.0724 AC: 416 AN: 5742

European-Non Finnish (NFE) AF: 0.144 AC: 159492 AN: 1105364

Other (OTH) AF: 0.117 AC: 7025 AN: 60102

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

African (AFR) AF: 0.0375 AC: 1557 AN: 41556

American (AMR) AF: 0.117 AC: 1786 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3470

East Asian (EAS) AF: 0.0710 AC: 368 AN: 5182

South Asian (SAS) AF: 0.108 AC: 520 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1573 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9638 AN: 67996

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.105 Hom.: 255

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
PhyloP100		-0.71
PromoterAI		0.081	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12448654; hg19: chr16-56701827; COSMIC: COSV60091328; COSMIC: COSV60091328;