12-6750721-C-T

Position:

• chr12-6750721-C-T

Variant summary

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

The NM_001382226.1(MLF2):​c.262G>A​(p.Gly88Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MLF2 NM_001382226.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52

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 (HGNC:):

ACMG classification

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
MLF2	NM_001382226.1	c.262G>A	p.Gly88Arg	missense_variant	5/9	ENST00000203630.10	NP_001369155.1
MLF2	NM_001382225.1	c.262G>A	p.Gly88Arg	missense_variant	5/8		NP_001369154.1
MLF2	NM_005439.3	c.262G>A	p.Gly88Arg	missense_variant	5/9		NP_005430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLF2	ENST00000203630.10	c.262G>A	p.Gly88Arg	missense_variant	5/9	1	NM_001382226.1	ENSP00000203630.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251362 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135846

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

May 26, 2023

The c.262G>A (p.G88R) alteration is located in exon 5 (coding exon 4) of the MLF2 gene. This alteration results from a G to A substitution at nucleotide position 262, causing the glycine (G) at amino acid position 88 to be replaced by an arginine (R). 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	0.83
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.034	T;T;T;T;T;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	.;D;.;.;D;D
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.44	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N;N;N;N;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.22	N;N;N;N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.77	T;T;T;T;T;T
Sift4G	Benign	0.79	T;T;T;T;.;.
Polyphen		0.76	P;P;P;P;.;.
Vest4		0.73
MutPred		0.53		Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);
MVP		0.27
MPC		0.90
ClinPred		0.70	D
GERP RS		5.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.20
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs755491031; hg19: chr12-6859887;