Variant chr1-93133949-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007358.4(MTF2):c.1288A>G(p.Asn430Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,427,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MTF2
NM_007358.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Variant links:

Genes affected

MTF2 (HGNC:29535): (metal response element binding transcription factor 2) Enables methylated histone binding activity and transcription corepressor binding activity. Predicted to be involved in several processes, including regulation of histone H3-K27 methylation; regulation of transcription by RNA polymerase II; and segment specification. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Located in cytoplasm; focal adhesion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MTF2 links:

MTF2 (HGNC:):

MTF2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14534861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF2	NM_007358.4 linkuse as main transcript	c.1288A>G	p.Asn430Asp	missense_variant	13/15	ENST00000370298.9	NP_031384.1	Q9Y483-1Q7Z534
MTF2	NM_001164392.2 linkuse as main transcript	c.1117A>G	p.Asn373Asp	missense_variant	12/14		NP_001157864.1	Q9Y483-4
MTF2	NM_001164391.2 linkuse as main transcript	c.982A>G	p.Asn328Asp	missense_variant	14/16		NP_001157863.1	Q9Y483-3B4DZG1B4DZ69
MTF2	NM_001164393.2 linkuse as main transcript	c.982A>G	p.Asn328Asp	missense_variant	11/13		NP_001157865.1	Q9Y483-3B4DZG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTF2	ENST00000370298.9 linkuse as main transcript	c.1288A>G	p.Asn430Asp	missense_variant	13/15	1	NM_007358.4	ENSP00000359321.4		Q9Y483-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245352

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1427792

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

711616

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.22e-7

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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 20, 2023

The c.1288A>G (p.N430D) alteration is located in exon 13 (coding exon 13) of the MTF2 gene. This alteration results from a A to G substitution at nucleotide position 1288, causing the asparagine (N) at amino acid position 430 to be replaced by an aspartic acid (D). 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

0.072

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

.;.;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.072

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

.;T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

.;.;L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.075

T;T;T;T

Sift4G

Benign

0.099

T;T;T;T

Polyphen

0.036

.;.;B;.

Vest4

0.27

MutPred

0.14

.;.;Gain of glycosylation at S428 (P = 0.0933);.;

MVP

0.49

MPC

0.41

ClinPred

0.41

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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