chr17-58982945-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2
The NM_014906.5(PPM1E):c.*1914C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,568,672 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0091 ( 25 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 19 hom. )
Consequence
PPM1E
NM_014906.5 3_prime_UTR
NM_014906.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.29
Genes affected
PPM1E (HGNC:19322): (protein phosphatase, Mg2+/Mn2+ dependent 1E) This gene encodes a member of the PPM family of serine/threonine-protein phosphatases. The encoded protein is localized to the nucleus and dephosphorylates and inactivates multiple substrates including serine/threonine-protein kinase PAK 1, 5'-AMP-activated protein kinase (AMPK) and the multifunctional calcium/calmodulin-dependent protein kinases. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]
TRIM37 (HGNC:7523): (tripartite motif containing 37) This gene encodes a member of the tripartite motif (TRIM) family, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. The RING finger and B-box domains chelate zinc and might be involved in protein-protein and/or protein-nucleic acid interactions. Mutations in this gene are associated with mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder that involves several tissues of mesodermal origin. TRIM37 localizes in peroxisomal membranes, and has been implicated in human peroxisomal biogenesis disorders. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.12).
BP6
?
Variant 17-58982945-C-T is Benign according to our data. Variant chr17-58982945-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1197064.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00906 (1377/151988) while in subpopulation AFR AF= 0.0307 (1273/41432). AF 95% confidence interval is 0.0293. There are 25 homozygotes in gnomad4. There are 670 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1372 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPM1E | NM_014906.5 | c.*1914C>T | 3_prime_UTR_variant | 7/7 | ENST00000308249.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPM1E | ENST00000308249.4 | c.*1914C>T | 3_prime_UTR_variant | 7/7 | 1 | NM_014906.5 | P1 | ||
TRIM37 | ENST00000393066.7 | c.2892-24G>A | intron_variant | 1 | P1 | ||||
TRIM37 | ENST00000583945.5 | c.160-24G>A | intron_variant | 3 | |||||
TRIM37 | ENST00000585287.5 | c.351-24G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00903 AC: 1372AN: 151870Hom.: 25 Cov.: 32
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GnomAD3 exomes AF: 0.00214 AC: 393AN: 183662Hom.: 5 AF XY: 0.00172 AC XY: 168AN XY: 97616
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GnomAD4 exome AF: 0.00107 AC: 1509AN: 1416684Hom.: 19 Cov.: 29 AF XY: 0.000968 AC XY: 678AN XY: 700566
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GnomAD4 genome ? AF: 0.00906 AC: 1377AN: 151988Hom.: 25 Cov.: 32 AF XY: 0.00902 AC XY: 670AN XY: 74294
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 18, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at