Variant 1-37823790-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.1091C>T(p.Thr364Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00482 in 1,613,962 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 27 hom. )

Consequence

MTF1
NM_005955.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.10

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=0.004799485).

BP6

Variant 1-37823790-G-A is Benign according to our data. Variant chr1-37823790-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 715469.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 420 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTF1	NM_005955.3 linkuse as main transcript	c.1091C>T	p.Thr364Ile	missense_variant	8/11	ENST00000373036.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTF1	ENST00000373036.5 linkuse as main transcript	c.1091C>T	p.Thr364Ile	missense_variant	8/11	1	NM_005955.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

420

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00498

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00251

AC:

630

AN:

251398

Hom.:

AF XY:

0.00253

AC XY:

344

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00503

AC:

7356

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

3626

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.00609

Gnomad4 OTH exome

AF:

0.00517

GnomAD4 genome

AF:

0.00276

AC:

420

AN:

152296

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00498

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00448

Hom.:

Bravo

AF:

0.00284

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00247

AC:

300

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00421

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

M_CAP

Benign

0.0094

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.95

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.8

REVEL

Benign

0.074

Sift

Benign

0.043

Sift4G

Benign

0.23

Polyphen

0.88

Vest4

0.51

MVP

0.26

MPC

0.58

ClinPred

0.031

GERP RS

5.3

Varity_R

0.10

gMVP

0.44

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