rs3912368

Positions:

• chr1-37835578-A-G

Variant summary

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

The NM_005955.3(MTF1):​c.853+93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 928,554 control chromosomes in the GnomAD database, including 214,439 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 0.60 (28763 hom., cov: 31)
  • Exomes 𝑓: 0.69 (185676 hom.)
• Consequence: MTF1 NM_005955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF1	NM_005955.3	c.853+93T>C		intron_variant		ENST00000373036.5	NP_005946.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5	c.853+93T>C		intron_variant		1	NM_005955.3	ENSP00000362127.3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90396 AN: 151832 Hom.: 28752 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.686 AC: 532764 AN: 776604 Hom.: 185676 AF XY: 0.684 AC XY: 278641 AN XY: 407360

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.557

Gnomad4 SAS exome AF: 0.602

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.721

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.595 AC: 90438 AN: 151950 Hom.: 28763 Cov.: 31 AF XY: 0.597 AC XY: 44335 AN XY: 74288

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.610

Alfa AF: 0.644 Hom.: 4096

Bravo AF: 0.565

Asia WGS AF: 0.557 AC: 1935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.23

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: rs3912368; hg19: chr1-38301250; COSMIC: COSV65989360;