rs12315

Variant names:

• chr16-56666810-G-T
• rs12315
• NM_001301267.2:c.*69C>A

Variant summary

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

The NM_001301267.2(MT1G):​c.*69C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,584,032 control chromosomes in the GnomAD database, including 6,045 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 0.081 (704 hom., cov: 33)
  • Exomes 𝑓: 0.075 (5341 hom.)
• Consequence: MT1G NM_001301267.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT1G	NM_001301267.2	c.*69C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000379811.4	NP_001288196.1
MT1G	NM_005950.3	c.*69C>A		3_prime_UTR_variant	Exon 3 of 3		NP_005941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT1G	ENST00000379811	c.*69C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001301267.2	ENSP00000369139.4
MT1G	ENST00000444837	c.*69C>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000391397.2
MT1G	ENST00000568675.1	n.624C>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
MT1G	ENST00000569500.5	c.*69C>A		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000456675.1

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12248 AN: 152152 Hom.: 701 Cov.: 33

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0864

GnomAD4 exome AF: 0.0752 AC: 107656 AN: 1431762 Hom.: 5341 Cov.: 30 AF XY: 0.0758 AC XY: 53806 AN XY: 710272

Gnomad4 AFR exome AF: 0.0557

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.0836

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0345

Gnomad4 NFE exome AF: 0.0632

Gnomad4 OTH exome AF: 0.0815

GnomAD4 genome AF: 0.0805 AC: 12265 AN: 152270 Hom.: 704 Cov.: 33 AF XY: 0.0836 AC XY: 6223 AN XY: 74444

Gnomad4 AFR AF: 0.0579

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0334

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.0888

Alfa AF: 0.0639 Hom.: 140

Bravo AF: 0.0900

Asia WGS AF: 0.164 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.16
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12315; hg19: chr16-56700722; COSMIC: COSV60090879; COSMIC: COSV60090879;