chr17-81956747-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_178493.6(NOTUM):c.891C>T(p.Tyr297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,612,034 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0035 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0045 ( 22 hom. )
Consequence
NOTUM
NM_178493.6 synonymous
NM_178493.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.17
Genes affected
NOTUM (HGNC:27106): (notum, palmitoleoyl-protein carboxylesterase) Enables palmitoleyl hydrolase activity. Involved in negative regulation of Wnt signaling pathway and protein depalmitoleylation. Acts upstream of or within bone development and regulation of bone mineralization. Predicted to be located in endoplasmic reticulum lumen and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
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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=-0.53).
BP6
Variant 17-81956747-G-A is Benign according to our data. Variant chr17-81956747-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648476.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.17 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 22 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTUM | NM_178493.6 | c.891C>T | p.Tyr297= | synonymous_variant | 8/11 | ENST00000409678.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTUM | ENST00000409678.8 | c.891C>T | p.Tyr297= | synonymous_variant | 8/11 | 1 | NM_178493.6 | P1 | |
NOTUM | ENST00000477214.5 | c.465C>T | p.Tyr155= | synonymous_variant | 7/8 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00352 AC: 536AN: 152196Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00247 AC: 609AN: 246122Hom.: 2 AF XY: 0.00247 AC XY: 331AN XY: 134142
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GnomAD4 exome AF: 0.00449 AC: 6549AN: 1459720Hom.: 22 Cov.: 31 AF XY: 0.00441 AC XY: 3202AN XY: 726208
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GnomAD4 genome AF: 0.00352 AC: 536AN: 152314Hom.: 1 Cov.: 33 AF XY: 0.00328 AC XY: 244AN XY: 74474
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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 | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | NOTUM: BP4, BP7 - |
Computational scores
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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