dbSNP rs3790625: MTF1:c.779+42G>C (chr1-37838583-C-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.779+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,570,402 control chromosomes in the GnomAD database, including 1,129 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 0.017 ( 172 hom., cov: 31)

Exomes 𝑓: 0.014 ( 957 hom. )

Consequence

MTF1
NM_005955.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.292

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=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTF1	NM_005955.3 link	c.779+42G>C		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.779+42G>C		intron_variant	Intron 4 of 10	1	NM_005955.3	ENSP00000362127.3		Q14872

Frequencies

GnomAD3 genomes

AF:

0.0168

AC:

2558

AN:

151936

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.00820

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00990

Gnomad OTH

AF:

0.0135

GnomAD2 exomes

AF:

0.0274

AC:

6625

AN:

242042

AF XY:

0.0266

show subpopulations

Gnomad AFR exome

AF:

0.00373

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0143

AC:

20266

AN:

1418348

Hom.:

957

Cov.:

AF XY:

0.0145

AC XY:

10251

AN XY:

705524

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

32520

American (AMR)

AF:

0.00344

AC:

143

AN:

41566

Ashkenazi Jewish (ASJ)

AF:

0.0111

AC:

277

AN:

24988

East Asian (EAS)

AF:

0.189

AC:

7285

AN:

38646

South Asian (SAS)

AF:

0.0209

AC:

1740

AN:

83140

European-Finnish (FIN)

AF:

0.0146

AC:

746

AN:

51110

Middle Eastern (MID)

AF:

0.00907

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.00792

AC:

8576

AN:

1082448

Other (OTH)

AF:

0.0236

AC:

1375

AN:

58306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

750

1501

2251

3002

3752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.0168

AC:

2555

AN:

152054

Hom.:

172

Cov.:

AF XY:

0.0183

AC XY:

1359

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00371

AC:

154

AN:

41514

American (AMR)

AF:

0.00819

AC:

125

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3470

East Asian (EAS)

AF:

0.233

AC:

1200

AN:

5160

South Asian (SAS)

AF:

0.0328

AC:

158

AN:

4820

European-Finnish (FIN)

AF:

0.0143

AC:

151

AN:

10550

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00989

AC:

672

AN:

67978

Other (OTH)

AF:

0.0138

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

113

227

340

454

567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0109

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.110

AC:

383

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.29

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