dbSNP rs3762359: MTF1:c.780-60C>T (chr1-37835804-G-A) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.512

Publications

7 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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTF1	NM_005955.3 link	c.780-60C>T		intron_variant	Intron 4 of 10	ENST00000373036.5	NP_005946.2	Q14872

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5 link	c.780-60C>T		intron_variant	Intron 4 of 10	1	NM_005955.3	ENSP00000362127.3		Q14872

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90007

AN:

151372

Hom.:

28585

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

10904

21808

32713

43617

54521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12832

25664

38496

51328

64160

<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:

0.594

AC:

90048

AN:

151488

Hom.:

28596

Cov.:

AF XY:

0.596

AC XY:

44108

AN XY:

73984

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1661

3322

4983

6644

8305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.620

Hom.:

4500

Bravo

AF:

0.563

Asia WGS

AF:

0.555

AC:

1926

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.3

(source)

DANN

Benign

0.49

PhyloP100

0.51

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over