1-93133783-T-A

Position:

• chr1-93133783-T-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_007358.4(MTF2):​c.1241T>A​(p.Ile414Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,458,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.000014 (0 hom.)
• Consequence: MTF2 NM_007358.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38611743).
• BS2: High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF2	NM_007358.4	c.1241T>A	p.Ile414Asn	missense_variant	12/15	ENST00000370298.9	NP_031384.1
MTF2	NM_001164392.2	c.1070T>A	p.Ile357Asn	missense_variant	11/14		NP_001157864.1
MTF2	NM_001164391.2	c.935T>A	p.Ile312Asn	missense_variant	13/16		NP_001157863.1
MTF2	NM_001164393.2	c.935T>A	p.Ile312Asn	missense_variant	10/13		NP_001157865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTF2	ENST00000370298.9	c.1241T>A	p.Ile414Asn	missense_variant	12/15	1	NM_007358.4	ENSP00000359321.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1458756 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 725728

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2024

The c.1241T>A (p.I414N) alteration is located in exon 12 (coding exon 12) of the MTF2 gene. This alteration results from a T to A substitution at nucleotide position 1241, causing the isoleucine (I) at amino acid position 414 to be replaced by an asparagine (N). 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	0.24
BayesDel_addAF	Benign	0.0039	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	.;.;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.073
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	.;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;.;N;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.028	D;D;T;T
Sift4G	Benign	0.093	T;T;T;T
Polyphen		0.12	.;.;B;.
Vest4		0.67
MVP		0.23
MPC		0.57
ClinPred		0.83	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-93599340;