chr1-15684609-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_015164.4(PLEKHM2):c.51G>A(p.Ser17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,303,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000067 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
PLEKHM2
NM_015164.4 synonymous
NM_015164.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.0360
Genes affected
PLEKHM2 (HGNC:29131): (pleckstrin homology and RUN domain containing M2) This gene encodes a protein that binds the plus-end directed microtubule motor protein kinesin, together with the lysosomal GTPase Arl8, and is required for lysosomes to distribute away from the microtubule-organizing center. The encoded protein belongs to the multisubunit BLOC-one-related complex that regulates lysosome positioning. It binds a Salmonella effector protein called Salmonella induced filament A and is a critical host determinant in Salmonella pathogenesis. It has a domain architecture consisting of an N-terminal RPIP8, UNC-14, and NESCA (RUN) domain that binds kinesin-1 as well as the lysosomal GTPase Arl8, and a C-terminal pleckstrin homology domain that binds the Salmonella induced filament A effector protein. Naturally occurring mutations in this gene lead to abnormal localization of lysosomes, impaired autophagy flux and are associated with recessive dilated cardiomyopathy and left ventricular noncompaction. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 1-15684609-G-A is Benign according to our data. Variant chr1-15684609-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 772520.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.036 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEKHM2 | NM_015164.4 | c.51G>A | p.Ser17= | synonymous_variant | 1/20 | ENST00000375799.8 | NP_055979.2 | |
PLEKHM2 | NM_001410755.1 | c.51G>A | p.Ser17= | synonymous_variant | 1/19 | NP_001397684.1 | ||
PLEKHM2 | XM_017000757.1 | c.99+2910G>A | intron_variant | XP_016856246.1 | ||||
PLEKHM2 | XM_017000758.1 | c.99+2910G>A | intron_variant | XP_016856247.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEKHM2 | ENST00000375799.8 | c.51G>A | p.Ser17= | synonymous_variant | 1/20 | 1 | NM_015164.4 | ENSP00000364956 | P2 | |
PLEKHM2 | ENST00000375793.2 | c.51G>A | p.Ser17= | synonymous_variant | 1/19 | 5 | ENSP00000364950 | A2 | ||
PLEKHM2 | ENST00000642363.1 | c.51G>A | p.Ser17= | synonymous_variant | 1/21 | ENSP00000494591 | A2 | |||
PLEKHM2 | ENST00000462455.1 | n.69G>A | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000665 AC: 10AN: 150372Hom.: 0 Cov.: 30
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GnomAD4 exome AF: 0.000145 AC: 167AN: 1152744Hom.: 0 Cov.: 29 AF XY: 0.000144 AC XY: 81AN XY: 561272
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GnomAD4 genome AF: 0.0000665 AC: 10AN: 150372Hom.: 0 Cov.: 30 AF XY: 0.0000409 AC XY: 3AN XY: 73430
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dilated Cardiomyopathy, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 09, 2024 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at