1-43337905-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_005373.3(MPL):c.57C>A(p.Asn19Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,609,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005373.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPL | NM_005373.3 | c.57C>A | p.Asn19Lys | missense_variant | 1/12 | ENST00000372470.9 | NP_005364.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPL | ENST00000372470.9 | c.57C>A | p.Asn19Lys | missense_variant | 1/12 | 1 | NM_005373.3 | ENSP00000361548.3 | ||
MPL | ENST00000413998.7 | c.57C>A | p.Asn19Lys | missense_variant | 1/12 | 1 | ENSP00000414004.3 | |||
MPL | ENST00000638732.1 | n.57C>A | non_coding_transcript_exon_variant | 1/10 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000952 AC: 23AN: 241550Hom.: 0 AF XY: 0.0000996 AC XY: 13AN XY: 130568
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1457118Hom.: 0 Cov.: 33 AF XY: 0.0000207 AC XY: 15AN XY: 724500
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.57C>A (p.N19K) alteration is located in exon 1 (coding exon 1) of the MPL gene. This alteration results from a C to A substitution at nucleotide position 57, causing the asparagine (N) at amino acid position 19 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Essential thrombocythemia;C1327915:Congenital amegakaryocytic thrombocytopenia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 24, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at