chr17-45437861-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_014798.3(PLEKHM1):c.3168C>T(p.Ala1056=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,613,232 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 5 hom. )
Consequence
PLEKHM1
NM_014798.3 synonymous
NM_014798.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.50
Genes affected
PLEKHM1 (HGNC:29017): (pleckstrin homology and RUN domain containing M1) The protein encoded by this gene is essential for bone resorption, and may play a critical role in vesicular transport in the osteoclast. Mutations in this gene are associated with autosomal recessive osteopetrosis type 6 (OPTB6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 17-45437861-G-A is Benign according to our data. Variant chr17-45437861-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1285181.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-45437861-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.5 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHM1 | NM_014798.3 | c.3168C>T | p.Ala1056= | synonymous_variant | 12/12 | ENST00000430334.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHM1 | ENST00000430334.8 | c.3168C>T | p.Ala1056= | synonymous_variant | 12/12 | 1 | NM_014798.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00102 AC: 156AN: 152276Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00149 AC: 375AN: 251064Hom.: 1 AF XY: 0.00160 AC XY: 217AN XY: 135864
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GnomAD4 exome AF: 0.00221 AC: 3223AN: 1460838Hom.: 5 Cov.: 31 AF XY: 0.00214 AC XY: 1554AN XY: 726820
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
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Benign
Cadd
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at