rs3790625

Positions:

• chr1-37838583-C-G

Variant summary

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

The NM_005955.3(MTF1):​c.779+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,570,402 control chromosomes in the GnomAD database, including 1,129 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 0.017 (172 hom., cov: 31)
  • Exomes 𝑓: 0.014 (957 hom.)
• Consequence: MTF1 NM_005955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTF1	NM_005955.3	c.779+42G>C		intron_variant		ENST00000373036.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTF1	ENST00000373036.5	c.779+42G>C		intron_variant		1	NM_005955.3	P1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2558 AN: 151936 Hom.: 173 Cov.: 31

Gnomad AFR AF: 0.00372

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.00820

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00990

Gnomad OTH AF: 0.0135

GnomAD3 exomes AF: 0.0274 AC: 6625 AN: 242042 Hom.: 555 AF XY: 0.0266 AC XY: 3497 AN XY: 131288

Gnomad AFR exome AF: 0.00373

Gnomad AMR exome AF: 0.00311

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.233

Gnomad SAS exome AF: 0.0229

Gnomad FIN exome AF: 0.0137

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.0209

GnomAD4 exome AF: 0.0143 AC: 20266 AN: 1418348 Hom.: 957 Cov.: 27 AF XY: 0.0145 AC XY: 10251 AN XY: 705524

Gnomad4 AFR exome AF: 0.00224

Gnomad4 AMR exome AF: 0.00344

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.0209

Gnomad4 FIN exome AF: 0.0146

Gnomad4 NFE exome AF: 0.00792

Gnomad4 OTH exome AF: 0.0236

GnomAD4 genome AF: 0.0168 AC: 2555 AN: 152054 Hom.: 172 Cov.: 31 AF XY: 0.0183 AC XY: 1359 AN XY: 74334

Gnomad4 AFR AF: 0.00371

Gnomad4 AMR AF: 0.00819

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.00989

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.0109 Hom.: 5

Bravo AF: 0.0172

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.65

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: rs3790625; hg19: chr1-38304255; COSMIC: COSV65990569; COSMIC: COSV65990569;