MLF1 p.Ser205Cys

Variant names:

• chr3-158600173-A-T
• NM_001369783.1:c.613A>T
• MLF1 p.Ser205Cys

Your query was ambiguous. Multiple possible variants found:

• chr3-158600173-A-T
• chr3-158600173-AGT-TGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001369783.1(MLF1):​c.613A>T​(p.Ser205Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S205S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MLF1 NM_001369783.1 missense, splice_region
• Scores: Splicing: ADA: 0.0004137
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 0 publications found

Genes affected

MLF1 (HGNC:7125): (myeloid leukemia factor 1) This gene encodes an oncoprotein which is thought to play a role in the phenotypic determination of hemopoetic cells. Translocations between this gene and nucleophosmin have been associated with myelodysplastic syndrome and acute myeloid leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2082057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369783.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLF1	NM_001369783.1	MANE Select	c.613A>T	p.Ser205Cys	missense splice_region	Exon 6 of 8	NP_001356712.1	A0A0S2Z4A4
	MLF1	NM_022443.5		c.568A>T	p.Ser190Cys	missense splice_region	Exon 5 of 7	NP_071888.1	A0A0S2Z4U8
	MLF1	NM_001378845.1		c.568A>T	p.Ser190Cys	missense splice_region	Exon 5 of 7	NP_001365774.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLF1	ENST00000466246.7	TSL:2 MANE Select	c.613A>T	p.Ser205Cys	missense splice_region	Exon 6 of 8	ENSP00000417278.2	A0A0S2Z4A4
	MLF1	ENST00000355893.11	TSL:1	c.568A>T	p.Ser190Cys	missense splice_region	Exon 5 of 7	ENSP00000348157.5	P58340-1
	MLF1	ENST00000359117.9	TSL:1	c.493A>T	p.Ser165Cys	missense splice_region	Exon 5 of 7	ENSP00000352025.5	P58340-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.28
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.094
Sift	Benign	0.064	T
Sift4G	Benign	0.077	T
Varity_R		0.13
gMVP		0.24
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00041
dbscSNV1_RF	Benign	0.086
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-158317962;