rs1172713973
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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.2109C>T(p.Ile703=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,108 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 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PLEKHM2
NM_015164.4 synonymous
NM_015164.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.911
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=-0.29).
BP6
?
Variant 1-15729830-C-T is Benign according to our data. Variant chr1-15729830-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 478076.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.911 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHM2 | NM_015164.4 | c.2109C>T | p.Ile703= | synonymous_variant | 14/20 | ENST00000375799.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHM2 | ENST00000375799.8 | c.2109C>T | p.Ile703= | synonymous_variant | 14/20 | 1 | NM_015164.4 | P2 | |
ENST00000453804.1 | n.211+2557G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248766Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135046
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460904Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726758
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74354
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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 | Invitae | May 22, 2023 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at