dbSNP rs3748682: MTF1:c.*821A>G (chr1-37814315-T-C) – 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.*821A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,058 control chromosomes in the GnomAD database, including 4,985 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 0.24 ( 4980 hom., cov: 32)

Exomes 𝑓: 0.33 ( 5 hom. )

Consequence

MTF1
NM_005955.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.430

Publications

37 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MTF1	NM_005955.3 link	c.*821A>G	3_prime_UTR_variant	Exon 11 of 11	ENST00000373036.5	NP_005946.2	Q14872
MTF1	XM_011541491.3 link	c.*821A>G	3_prime_UTR_variant	Exon 11 of 11		XP_011539793.1	Q14872
MTF1	XM_047421170.1 link	c.*821A>G	3_prime_UTR_variant	Exon 12 of 12		XP_047277126.1
MTF1	XM_047421173.1 link	c.*821A>G	3_prime_UTR_variant	Exon 10 of 10		XP_047277129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5 link	c.*821A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_005955.3	ENSP00000362127.3		Q14872

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36434

AN:

151864

Hom.:

4979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.329

AC:

AN:

Hom.:

Cov.:

AF XY:

0.276

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.296

AC:

AN:

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.240

AC:

36430

AN:

151982

Hom.:

4980

Cov.:

AF XY:

0.245

AC XY:

18184

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.102

AC:

4240

AN:

41484

American (AMR)

AF:

0.216

AC:

3290

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1074

AN:

3460

East Asian (EAS)

AF:

0.276

AC:

1427

AN:

5166

South Asian (SAS)

AF:

0.262

AC:

1260

AN:

4810

European-Finnish (FIN)

AF:

0.395

AC:

4160

AN:

10532

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20350

AN:

67954

Other (OTH)

AF:

0.237

AC:

500

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1356

2713

4069

5426

6782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.229

Hom.:

16803

Bravo

AF:

0.217

Asia WGS

AF:

0.294

AC:

1020

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.37

(source)

DANN

Benign

0.51

PhyloP100

-0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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