Variant chr1-93136998-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007358.4(MTF2):c.1753G>A(p.Val585Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MTF2
NM_007358.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF2	NM_007358.4 linkuse as main transcript	c.1753G>A	p.Val585Met	missense_variant	15/15	ENST00000370298.9	NP_031384.1	Q9Y483-1Q7Z534
MTF2	NM_001164392.2 linkuse as main transcript	c.1582G>A	p.Val528Met	missense_variant	14/14		NP_001157864.1	Q9Y483-4
MTF2	NM_001164391.2 linkuse as main transcript	c.1447G>A	p.Val483Met	missense_variant	16/16		NP_001157863.1	Q9Y483-3B4DZG1B4DZ69
MTF2	NM_001164393.2 linkuse as main transcript	c.1447G>A	p.Val483Met	missense_variant	13/13		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.1753G>A	p.Val585Met	missense_variant	15/15	1	NM_007358.4	ENSP00000359321.4		Q9Y483-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 01, 2021

The c.1753G>A (p.V585M) alteration is located in exon 15 (coding exon 15) of the MTF2 gene. This alteration results from a G to A substitution at nucleotide position 1753, causing the valine (V) at amino acid position 585 to be replaced by a methionine (M). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.42

.;.;T;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

.;D;D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.1

.;.;M;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.71

MutPred

0.39

.;.;Gain of catalytic residue at V581 (P = 0.0292);.;

MVP

0.79

MPC

1.0

ClinPred

0.85

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.74

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