Variant chr1-93133977-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007358.4(MTF2):c.1316T>C(p.Ile439Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,571,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

MTF2
NM_007358.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029450685).

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF2	NM_007358.4 linkuse as main transcript	c.1316T>C	p.Ile439Thr	missense_variant	13/15	ENST00000370298.9	NP_031384.1	Q9Y483-1Q7Z534
MTF2	NM_001164392.2 linkuse as main transcript	c.1145T>C	p.Ile382Thr	missense_variant	12/14		NP_001157864.1	Q9Y483-4
MTF2	NM_001164391.2 linkuse as main transcript	c.1010T>C	p.Ile337Thr	missense_variant	14/16		NP_001157863.1	Q9Y483-3B4DZG1B4DZ69
MTF2	NM_001164393.2 linkuse as main transcript	c.1010T>C	p.Ile337Thr	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.1316T>C	p.Ile439Thr	missense_variant	13/15	1	NM_007358.4	ENSP00000359321.4		Q9Y483-1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000458

AC:

AN:

239960

Hom.:

AF XY:

0.0000462

AC XY:

AN XY:

129886

show subpopulations

Gnomad AFR exome

AF:

0.000645

Gnomad AMR exome

AF:

0.0000312

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000169

AC:

AN:

1419720

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

707660

show subpopulations

Gnomad4 AFR exome

AF:

0.000689

Gnomad4 AMR exome

AF:

0.0000238

Gnomad4 ASJ exome

AF:

0.0000393

Gnomad4 EAS exome

AF:

0.00

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

AF:

0.000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000482

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000337

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

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

Mar 29, 2022

The c.1316T>C (p.I439T) alteration is located in exon 13 (coding exon 13) of the MTF2 gene. This alteration results from a T to C substitution at nucleotide position 1316, causing the isoleucine (I) at amino acid position 439 to be replaced by a threonine (T). 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

0.052

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.14

.;.;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.029

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

.;.;N;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.33

N;N;N;N

REVEL

Benign

0.019

Sift

Benign

0.40

T;T;T;T

Sift4G

Benign

0.58

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.068

MVP

0.10

MPC

0.37

ClinPred

0.021

GERP RS

2.9

Varity_R

0.056

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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