chr17-45439623-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_014798.3(PLEKHM1):c.2913G>A(p.Gly971=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,613,956 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.025 ( 159 hom., cov: 33)
Exomes 𝑓: 0.0023 ( 132 hom. )
Consequence
PLEKHM1
NM_014798.3 synonymous
NM_014798.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.858
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 17-45439623-C-T is Benign according to our data. Variant chr17-45439623-C-T is described in ClinVar as [Benign]. Clinvar id is 1291719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.858 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHM1 | NM_014798.3 | c.2913G>A | p.Gly971= | synonymous_variant | 11/12 | ENST00000430334.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHM1 | ENST00000430334.8 | c.2913G>A | p.Gly971= | synonymous_variant | 11/12 | 1 | NM_014798.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0255 AC: 3878AN: 152078Hom.: 160 Cov.: 33
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GnomAD3 exomes AF: 0.00646 AC: 1624AN: 251394Hom.: 68 AF XY: 0.00495 AC XY: 673AN XY: 135894
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GnomAD4 exome AF: 0.00235 AC: 3434AN: 1461760Hom.: 132 Cov.: 32 AF XY: 0.00205 AC XY: 1490AN XY: 727174
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GnomAD4 genome AF: 0.0255 AC: 3879AN: 152196Hom.: 159 Cov.: 33 AF XY: 0.0246 AC XY: 1830AN XY: 74414
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Increased bone mineral density Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 13, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 10, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at