dbSNP rs3912368: MTF1:c.853+93T>C (chr1-37835578-A-G) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.600

Publications

4 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 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.853+93T>C		intron	N/A	NP_005946.2	Q14872

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTF1	ENST00000373036.5	TSL:1 MANE Select	c.853+93T>C	intron	N/A	ENSP00000362127.3	Q14872
MTF1	ENST00000880496.1		c.853+93T>C	intron	N/A	ENSP00000550555.1
MTF1	ENST00000880495.1		c.853+93T>C	intron	N/A	ENSP00000550554.1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90396

AN:

151832

Hom.:

28752

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.355

AC:

6894

AN:

19420

American (AMR)

AF:

0.581

AC:

21063

AN:

36274

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

13896

AN:

20758

East Asian (EAS)

AF:

0.557

AC:

19032

AN:

34182

South Asian (SAS)

AF:

0.602

AC:

41155

AN:

68402

European-Finnish (FIN)

AF:

0.777

AC:

39311

AN:

50592

Middle Eastern (MID)

AF:

0.605

AC:

2521

AN:

4164

European-Non Finnish (NFE)

AF:

0.721

AC:

364492

AN:

505248

Other (OTH)

AF:

0.650

AC:

24400

AN:

37564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

8196

16393

24589

32786

40982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5440

10880

16320

21760

27200

<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:

0.595

AC:

90438

AN:

151950

Hom.:

28763

Cov.:

AF XY:

0.597

AC XY:

44335

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.360

AC:

14889

AN:

41396

American (AMR)

AF:

0.595

AC:

9088

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

2294

AN:

3472

East Asian (EAS)

AF:

0.496

AC:

2562

AN:

5162

South Asian (SAS)

AF:

0.599

AC:

2885

AN:

4816

European-Finnish (FIN)

AF:

0.785

AC:

8298

AN:

10570

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.715

AC:

48573

AN:

67950

Other (OTH)

AF:

0.610

AC:

1289

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1672

3344

5015

6687

8359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.633

Hom.:

4142

Bravo

AF:

0.565

Asia WGS

AF:

0.557

AC:

1935

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.4

(source)

DANN

Benign

0.23

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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