chr1-43338669-G-A
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2
The NM_005373.3(MPL):c.340G>A(p.Val114Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,614,118 control chromosomes in the GnomAD database, including 766 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 Likely benign (★★).
Frequency
Consequence
NM_005373.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPL | ENST00000372470.9 | c.340G>A | p.Val114Met | missense_variant | Exon 3 of 12 | 1 | NM_005373.3 | ENSP00000361548.3 | ||
MPL | ENST00000413998.7 | c.319G>A | p.Val107Met | missense_variant | Exon 3 of 12 | 1 | ENSP00000414004.3 | |||
MPL | ENST00000638732.1 | n.340G>A | non_coding_transcript_exon_variant | Exon 3 of 10 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0223 AC: 3392AN: 152126Hom.: 48 Cov.: 32
GnomAD3 exomes AF: 0.0246 AC: 6191AN: 251490Hom.: 101 AF XY: 0.0262 AC XY: 3559AN XY: 135920
GnomAD4 exome AF: 0.0299 AC: 43742AN: 1461872Hom.: 718 Cov.: 32 AF XY: 0.0300 AC XY: 21851AN XY: 727242
GnomAD4 genome AF: 0.0223 AC: 3392AN: 152246Hom.: 48 Cov.: 32 AF XY: 0.0215 AC XY: 1602AN XY: 74434
ClinVar
Submissions by phenotype
not provided Benign:5
- -
- -
- -
- -
This variant is associated with the following publications: (PMID: 27884173, 11133753, 21228398, 24728327, 20981092, 22995991) -
Congenital amegakaryocytic thrombocytopenia Pathogenic:1Benign:3
- -
- -
- -
- -
not specified Benign:2Other:1
The p.Val114Met variant in MPL is classified as likely benign because it has been identified in 3.3% (2251/68026) of European chromosomes including 48 homozygotes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). In addition, computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1, BP4. -
- -
- -
Essential thrombocythemia;C1327915:Congenital amegakaryocytic thrombocytopenia Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at