chr8-100948629-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_145690.3(YWHAZ):c.261G>A(p.Glu87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,611,016 control chromosomes in the GnomAD database, including 2,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.038 ( 145 hom., cov: 32)
Exomes 𝑓: 0.055 ( 2410 hom. )
Consequence
YWHAZ
NM_145690.3 synonymous
NM_145690.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.36
Genes affected
YWHAZ (HGNC:12855): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse, rat and sheep orthologs. The encoded protein interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. Several transcript variants that differ in the 5' UTR but that encode the same protein have been identified for this gene. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 8-100948629-C-T is Benign according to our data. Variant chr8-100948629-C-T is described in ClinVar as [Benign]. Clinvar id is 1593463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.37 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
YWHAZ | NM_145690.3 | c.261G>A | p.Glu87= | synonymous_variant | 2/6 | ENST00000395958.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
YWHAZ | ENST00000395958.6 | c.261G>A | p.Glu87= | synonymous_variant | 2/6 | 1 | NM_145690.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0382 AC: 5813AN: 152194Hom.: 144 Cov.: 32
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GnomAD3 exomes AF: 0.0436 AC: 10910AN: 250304Hom.: 321 AF XY: 0.0452 AC XY: 6123AN XY: 135364
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GnomAD4 exome AF: 0.0550 AC: 80233AN: 1458704Hom.: 2410 Cov.: 32 AF XY: 0.0544 AC XY: 39479AN XY: 725708
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GnomAD4 genome AF: 0.0382 AC: 5814AN: 152312Hom.: 145 Cov.: 32 AF XY: 0.0368 AC XY: 2742AN XY: 74466
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
YWHAZ-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 04, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at