Variant chr1-37815258-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_005955.3(MTF1):c.2140G>T(p.Ala714Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MTF1
NM_005955.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MTF1. . Gene score misZ 2.5403 (greater than the threshold 3.09). Trascript score misZ 3.4658 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40.

BP4

Computational evidence support a benign effect (MetaRNN=0.05504647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF1	NM_005955.3 linkuse as main transcript	c.2140G>T	p.Ala714Ser	missense_variant	11/11	ENST00000373036.5	NP_005946.2	Q14872
MTF1	XM_011541491.3 linkuse as main transcript	c.2140G>T	p.Ala714Ser	missense_variant	11/11		XP_011539793.1	Q14872
MTF1	XM_047421170.1 linkuse as main transcript	c.2140G>T	p.Ala714Ser	missense_variant	12/12		XP_047277126.1
MTF1	XM_047421173.1 linkuse as main transcript	c.1213G>T	p.Ala405Ser	missense_variant	10/10		XP_047277129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5 linkuse as main transcript	c.2140G>T	p.Ala714Ser	missense_variant	11/11	1	NM_005955.3	ENSP00000362127.3		Q14872

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251486

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.2140G>T (p.A714S) alteration is located in exon 11 (coding exon 10) of the MTF1 gene. This alteration results from a G to T substitution at nucleotide position 2140, causing the alanine (A) at amino acid position 714 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.87

Eigen

Benign

-0.0010

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

M_CAP

Benign

0.0040

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.37

PROVEAN

Benign

0.070

REVEL

Benign

0.092

Sift

Benign

0.46

Sift4G

Benign

0.70

Polyphen

0.16

Vest4

0.073

MutPred

0.050

Gain of phosphorylation at A714 (P = 0.0287);

MVP

0.25

MPC

0.72

ClinPred

0.12

GERP RS

5.7

Varity_R

0.094

gMVP

0.13

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