dbSNP rs28411352: MTF1:c.*2229G>A (chr1-37812907-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

Publications

43 publications found

Variant links:

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

MTF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	NM_005955.3	MANE Select	c.*2229G>A		3_prime_UTR	Exon 11 of 11	NP_005946.2	Q14872

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	ENST00000373036.5	TSL:1 MANE Select	c.*2229G>A		3_prime_UTR	Exon 11 of 11	ENSP00000362127.3	Q14872

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35388

AN:

151958

Hom.:

4244

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.300

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.233

AC:

35425

AN:

152078

Hom.:

4254

Cov.:

AF XY:

0.234

AC XY:

17424

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.203

AC:

8435

AN:

41496

American (AMR)

AF:

0.268

AC:

4095

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

376

AN:

3468

East Asian (EAS)

AF:

0.216

AC:

1117

AN:

5172

South Asian (SAS)

AF:

0.198

AC:

954

AN:

4820

European-Finnish (FIN)

AF:

0.307

AC:

3241

AN:

10550

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16579

AN:

67976

Other (OTH)

AF:

0.220

AC:

464

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1378

2756

4134

5512

6890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.237

Hom.:

7513

Bravo

AF:

0.228

Asia WGS

AF:

0.197

AC:

686

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.4

(source)

DANN

Benign

0.56

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over