chr17-45450619-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4BP6_Moderate
The NM_014798.3(PLEKHM1):c.2642C>T(p.Pro881Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P881Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_014798.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHM1 | NM_014798.3 | c.2642C>T | p.Pro881Leu | missense_variant, splice_region_variant | 8/12 | ENST00000430334.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHM1 | ENST00000430334.8 | c.2642C>T | p.Pro881Leu | missense_variant, splice_region_variant | 8/12 | 1 | NM_014798.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152026Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250906Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135632
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461398Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 726986
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152026Hom.: 0 Cov.: 29 AF XY: 0.0000539 AC XY: 4AN XY: 74258
ClinVar
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | PLEKHM1: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at