rs28411352

chr1-37812907-C-T

Variant summary

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

The NM_005955.3(MTF1):c.*2229G>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 0.233 in 152,110 control chromosomes in the GnomAD database, including 4,255 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 0.23 (4254 hom., cov: 32)
  • Exomes 𝑓: 0.31 (1 hom.)
• Consequence: MTF1 NM_005955.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

Genes affected

MTF1 (HGNC:7428): (metal regulatory transcription factor 1) This gene encodes a transcription factor that induces expression of metallothioneins and other genes involved in metal homeostasis in response to heavy metals such as cadmium, zinc, copper, and silver. The protein is a nucleocytoplasmic shuttling protein that accumulates in the nucleus upon heavy metal exposure and binds to promoters containing a metal-responsive element (MRE). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTF1	NM_005955.3	c.*2229G>A		3_prime_UTR_variant	11/11	ENST00000373036.5
MTF1	XM_011541491.3	c.*2229G>A		3_prime_UTR_variant	11/11
MTF1	XM_047421170.1	c.*2229G>A		3_prime_UTR_variant	12/12
MTF1	XM_047421173.1	c.*2229G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTF1	ENST00000373036.5	c.*2229G>A		3_prime_UTR_variant	11/11	1	NM_005955.3	P1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35388 AN: 151958 Hom.: 4244 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.313 AC: 10 AN: 32 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 7 AN XY: 28

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.233 AC: 35425 AN: 152078 Hom.: 4254 Cov.: 32 AF XY: 0.234 AC XY: 17424 AN XY: 74322

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.220

Alfa AF: 0.232 Hom.: 1047

Bravo AF: 0.228

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	9.4
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs28411352; hg19: chr1-38278579;