1-37835804-G-A

Variant names:

• chr1-37835804-G-A
• rs3762359
• NM_005955.3:c.780-60C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005955.3(MTF1):​c.780-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,285,984 control chromosomes in the GnomAD database, including 308,009 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 0.59 (28596 hom., cov: 29)
  • Exomes 𝑓: 0.69 (279413 hom.)
• Consequence: MTF1 NM_005955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512
• Publications: 7 publications found

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]

MTF1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005955.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	NM_005955.3	MANE Select	c.780-60C>T		intron	N/A	NP_005946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	ENST00000373036.5	TSL:1 MANE Select	c.780-60C>T		intron	N/A	ENSP00000362127.3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90007 AN: 151372 Hom.: 28585 Cov.: 29

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.691 AC: 784271 AN: 1134496 Hom.: 279413 AF XY: 0.689 AC XY: 398213 AN XY: 577666

African (AFR) AF: 0.331 AC: 8812 AN: 26590

American (AMR) AF: 0.572 AC: 22218 AN: 38840

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 15785 AN: 23572

East Asian (EAS) AF: 0.549 AC: 20859 AN: 37960

South Asian (SAS) AF: 0.597 AC: 44679 AN: 74804

European-Finnish (FIN) AF: 0.778 AC: 39925 AN: 51302

Middle Eastern (MID) AF: 0.607 AC: 3062 AN: 5046

European-Non Finnish (NFE) AF: 0.722 AC: 596983 AN: 827214

Other (OTH) AF: 0.650 AC: 31948 AN: 49168

GnomAD4 genome AF: 0.594 AC: 90048 AN: 151488 Hom.: 28596 Cov.: 29 AF XY: 0.596 AC XY: 44108 AN XY: 73984

African (AFR) AF: 0.360 AC: 14848 AN: 41276

American (AMR) AF: 0.592 AC: 9020 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2294 AN: 3468

East Asian (EAS) AF: 0.499 AC: 2563 AN: 5134

South Asian (SAS) AF: 0.600 AC: 2876 AN: 4796

European-Finnish (FIN) AF: 0.785 AC: 8197 AN: 10440

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48421 AN: 67846

Other (OTH) AF: 0.607 AC: 1273 AN: 2098

Alfa AF: 0.620 Hom.: 4500

Bravo AF: 0.563

Asia WGS AF: 0.555 AC: 1926 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.49
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3762359; hg19: chr1-38301476;