Variant 12-6751947-G-A 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_001382226.1(MLF2):c.158C>T(p.Pro53Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MLF2
NM_001382226.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

MLF2 (HGNC:7126): (myeloid leukemia factor 2) Predicted to be involved in regulation of transcription, DNA-templated. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MLF2 links:

MLF2 (HGNC:):

MLF2 links:

Genome browser will be placed here

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=0.2260699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLF2	NM_001382226.1 linkuse as main transcript	c.158C>T	p.Pro53Leu	missense_variant	3/9	ENST00000203630.10	NP_001369155.1
MLF2	NM_001382225.1 linkuse as main transcript	c.158C>T	p.Pro53Leu	missense_variant	3/8		NP_001369154.1
MLF2	NM_005439.3 linkuse as main transcript	c.158C>T	p.Pro53Leu	missense_variant	3/9		NP_005430.1	Q15773Q5U0N1A8K1F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLF2	ENST00000203630.10 linkuse as main transcript	c.158C>T	p.Pro53Leu	missense_variant	3/9	1	NM_001382226.1	ENSP00000203630.5		Q15773

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

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

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251128

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135786

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727244

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 13, 2022

The c.158C>T (p.P53L) alteration is located in exon 3 (coding exon 2) of the MLF2 gene. This alteration results from a C to T substitution at nucleotide position 158, causing the proline (P) at amino acid position 53 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

0.0049

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.22

T;T;T;T;T;T;T

Eigen

Benign

0.099

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

.;D;.;.;D;D;D

M_CAP

Benign

0.0050

MetaRNN

Benign

0.23

T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

M;M;M;M;.;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

N;N;N;N;N;D;D

REVEL

Benign

0.080

Sift

Benign

0.055

T;T;T;T;D;T;D

Sift4G

Benign

0.20

T;T;T;T;.;.;.

Polyphen

0.32

B;B;B;B;.;.;.

Vest4

0.28

MutPred

0.52

Loss of glycosylation at P53 (P = 0.0127);Loss of glycosylation at P53 (P = 0.0127);Loss of glycosylation at P53 (P = 0.0127);Loss of glycosylation at P53 (P = 0.0127);Loss of glycosylation at P53 (P = 0.0127);Loss of glycosylation at P53 (P = 0.0127);Loss of glycosylation at P53 (P = 0.0127);

MVP

0.10

MPC

0.26

ClinPred

0.29

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.26

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