3-158600175-T-C

Variant names:

• chr3-158600175-T-C
• NM_001369783.1:c.613+2T>C

Variant summary

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

The NM_001369783.1(MLF1):​c.613+2T>C variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MLF1 NM_001369783.1 splice_donor, intron
• Scores: Splicing: ADA: 0.9947
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.613+2T>C		splice_donor intron	N/A	NP_001356712.1	A0A0S2Z4A4
	MLF1	NM_022443.5		c.568+2T>C		splice_donor intron	N/A	NP_071888.1	A0A0S2Z4U8
	MLF1	NM_001378845.1		c.568+2T>C		splice_donor intron	N/A	NP_001365774.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLF1	ENST00000466246.7	TSL:2 MANE Select	c.613+2T>C		splice_donor intron	N/A	ENSP00000417278.2	A0A0S2Z4A4
	MLF1	ENST00000355893.11	TSL:1	c.568+2T>C		splice_donor intron	N/A	ENSP00000348157.5	P58340-1
	MLF1	ENST00000359117.9	TSL:1	c.493+2T>C		splice_donor intron	N/A	ENSP00000352025.5	P58340-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1256966 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 619536

African (AFR) AF: 0.00 AC: 0 AN: 26098

American (AMR) AF: 0.00 AC: 0 AN: 22718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20146

East Asian (EAS) AF: 0.00 AC: 0 AN: 32442

South Asian (SAS) AF: 0.00 AC: 0 AN: 48690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4854

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1006016

Other (OTH) AF: 0.00 AC: 0 AN: 50542

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	30
DANN	Uncertain	0.99
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.5
Mutation Taster		=6/94	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Benign	0.67
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: -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: chr3-158317964;