rs3748682

Positions:

• chr1-37814315-T-C

Variant summary

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

The NM_005955.3(MTF1):​c.*821A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,058 control chromosomes in the GnomAD database, including 4,985 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 0.24 (4980 hom., cov: 32)
  • Exomes 𝑓: 0.33 (5 hom.)
• Consequence: MTF1 NM_005955.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF1	NM_005955.3	c.*821A>G		3_prime_UTR_variant	11/11	ENST00000373036.5	NP_005946.2
MTF1	XM_011541491.3	c.*821A>G		3_prime_UTR_variant	11/11		XP_011539793.1
MTF1	XM_047421170.1	c.*821A>G		3_prime_UTR_variant	12/12		XP_047277126.1
MTF1	XM_047421173.1	c.*821A>G		3_prime_UTR_variant	10/10		XP_047277129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5	c.*821A>G		3_prime_UTR_variant	11/11	1	NM_005955.3	ENSP00000362127	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36434 AN: 151864 Hom.: 4979 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.329 AC: 25 AN: 76 Hom.: 5 Cov.: 0 AF XY: 0.276 AC XY: 16 AN XY: 58

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.240 AC: 36430 AN: 151982 Hom.: 4980 Cov.: 32 AF XY: 0.245 AC XY: 18184 AN XY: 74272

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.237

Alfa AF: 0.236 Hom.: 6669

Bravo AF: 0.217

Asia WGS AF: 0.294 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs3748682; hg19: chr1-38279987; COSMIC: COSV65988619; COSMIC: COSV65988619;