rs2298846

chr16-56667403-A-G

Variant summary

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

The NM_001301267.2(MT1G):c.29-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 1,608,418 control chromosomes in the GnomAD database, including 2,068 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 0.051 (239 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1829 hom.)
• Consequence: MT1G NM_001301267.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MT1G	NM_001301267.2	c.29-23T>C		intron_variant		ENST00000379811.4
MT1G	NM_005950.3	c.29-26T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT1G	ENST00000379811.4	c.29-23T>C		intron_variant		1	NM_001301267.2	A1
MT1G	ENST00000444837.6	c.29-26T>C		intron_variant		1		P4
MT1G	ENST00000568675.1	n.57-26T>C		intron_variant, non_coding_transcript_variant		1
MT1G	ENST00000569500.5	c.29-433T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7598 AN: 149436 Hom.: 239 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.0288

Gnomad NFE AF: 0.0366

Gnomad OTH AF: 0.0426

GnomAD3 exomes AF: 0.0571 AC: 14318 AN: 250894 Hom.: 551 AF XY: 0.0561 AC XY: 7617 AN XY: 135688

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.0356

Gnomad EAS exome AF: 0.0534

Gnomad SAS exome AF: 0.0862

Gnomad FIN exome AF: 0.0553

Gnomad NFE exome AF: 0.0342

Gnomad OTH exome AF: 0.0471

GnomAD4 exome AF: 0.0446 AC: 64996 AN: 1458872 Hom.: 1829 Cov.: 32 AF XY: 0.0453 AC XY: 32912 AN XY: 725998

Gnomad4 AFR exome AF: 0.0581

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.0338

Gnomad4 EAS exome AF: 0.0710

Gnomad4 SAS exome AF: 0.0839

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.0368

Gnomad4 OTH exome AF: 0.0483

GnomAD4 genome AF: 0.0509 AC: 7609 AN: 149546 Hom.: 239 Cov.: 33 AF XY: 0.0525 AC XY: 3835 AN XY: 73116

Gnomad4 AFR AF: 0.0586

Gnomad4 AMR AF: 0.0877

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.0578

Gnomad4 SAS AF: 0.0789

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0365

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0455 Hom.: 29

Bravo AF: 0.0625

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.8
Dann	Benign	0.29

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: rs2298846; hg19: chr16-56701315; COSMIC: COSV60091159; COSMIC: COSV60091159;