rs117656396
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005373.3(MPL):c.793C>T(p.Leu265Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,614,182 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L265L) has been classified as Likely benign.
Frequency
Consequence
NM_005373.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPL | NM_005373.3 | c.793C>T | p.Leu265Phe | missense_variant | 5/12 | ENST00000372470.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPL | ENST00000372470.9 | c.793C>T | p.Leu265Phe | missense_variant | 5/12 | 1 | NM_005373.3 | P1 | |
MPL | ENST00000413998.7 | c.772C>T | p.Leu258Phe | missense_variant | 5/12 | 1 | |||
MPL | ENST00000638732.1 | n.793C>T | non_coding_transcript_exon_variant | 5/10 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000696 AC: 106AN: 152204Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00141 AC: 354AN: 251000Hom.: 2 AF XY: 0.00119 AC XY: 162AN XY: 135656
GnomAD4 exome AF: 0.000330 AC: 482AN: 1461860Hom.: 6 Cov.: 32 AF XY: 0.000281 AC XY: 204AN XY: 727234
GnomAD4 genome ? AF: 0.000696 AC: 106AN: 152322Hom.: 1 Cov.: 33 AF XY: 0.000779 AC XY: 58AN XY: 74484
ClinVar
Submissions by phenotype
Congenital amegakaryocytic thrombocytopenia Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 16, 2017 | - - |
not specified Benign:1Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 26, 2019 | - - |
Essential thrombocythemia;C1327915:Congenital amegakaryocytic thrombocytopenia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at