Variant 1-37822570-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_005955.3(MTF1):c.1318C>T(p.Pro440Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,614,064 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 2 hom. )

Consequence

MTF1
NM_005955.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.48

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, MTF1

BP4

Computational evidence support a benign effect (MetaRNN=0.0042310357).

BP6

Variant 1-37822570-G-A is Benign according to our data. Variant chr1-37822570-G-A is described in ClinVar as [Benign]. Clinvar id is 769238.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 665 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTF1	NM_005955.3 linkuse as main transcript	c.1318C>T	p.Pro440Ser	missense_variant	9/11	ENST00000373036.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTF1	ENST00000373036.5 linkuse as main transcript	c.1318C>T	p.Pro440Ser	missense_variant	9/11	1	NM_005955.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

665

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00111

AC:

278

AN:

250918

Hom.:

AF XY:

0.000796

AC XY:

108

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.0158

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000407

AC:

595

AN:

1461816

Hom.:

Cov.:

AF XY:

0.000334

AC XY:

243

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0153

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.00438

AC:

667

AN:

152248

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

324

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.000695

Hom.:

Bravo

AF:

0.00482

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00137

AC:

166

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

Cadd

Benign

Dann

Benign

0.87

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.62

PrimateAI

Benign

0.42

PROVEAN

Benign

0.17

REVEL

Benign

0.030

Sift

Benign

0.44

Sift4G

Benign

0.96

Polyphen

0.0080

Vest4

0.19

MVP

0.15

MPC

0.26

ClinPred

0.0033

GERP RS

3.3

Varity_R

0.032

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over