chr10-97748335-G-A
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001385875.1(ZFYVE27):c.522G>A(p.Leu174=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00059 ( 1 hom. )
Consequence
ZFYVE27
NM_001385875.1 synonymous
NM_001385875.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.137
Genes affected
ZFYVE27 (HGNC:26559): (zinc finger FYVE-type containing 27) This gene encodes a protein with several transmembrane domains, a Rab11-binding domain and a lipid-binding FYVE finger domain. The encoded protein appears to promote neurite formation. A mutation in this gene has been reported to be associated with hereditary spastic paraplegia, however the pathogenicity of the mutation, which may simply represent a polymorphism, is unclear. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 10-97748335-G-A is Benign according to our data. Variant chr10-97748335-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 301835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.137 with no splicing effect.
BS2
High AC in GnomAd4 at 50 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE27 | NM_001385875.1 | c.522G>A | p.Leu174= | synonymous_variant | 5/13 | ENST00000684270.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE27 | ENST00000684270.1 | c.522G>A | p.Leu174= | synonymous_variant | 5/13 | NM_001385875.1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000329 AC: 50AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000371 AC: 93AN: 250962Hom.: 0 AF XY: 0.000361 AC XY: 49AN XY: 135684
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GnomAD4 exome AF: 0.000588 AC: 860AN: 1461826Hom.: 1 Cov.: 31 AF XY: 0.000587 AC XY: 427AN XY: 727220
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GnomAD4 genome AF: 0.000328 AC: 50AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74466
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 33 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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