rs34952009
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_015346.4(ZFYVE26):c.5678G>T(p.Ser1893Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00821 in 1,614,132 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1893G) has been classified as Uncertain significance.
Frequency
Consequence
NM_015346.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.5678G>T | p.Ser1893Ile | missense_variant | 31/42 | ENST00000347230.9 | |
ZFYVE26 | XM_047431173.1 | c.5678G>T | p.Ser1893Ile | missense_variant | 31/42 | ||
ZFYVE26 | XM_047431174.1 | c.3353G>T | p.Ser1118Ile | missense_variant | 20/31 | ||
ZFYVE26 | XM_047431175.1 | c.3260G>T | p.Ser1087Ile | missense_variant | 20/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.5678G>T | p.Ser1893Ile | missense_variant | 31/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00702 AC: 1068AN: 152138Hom.: 5 Cov.: 31
GnomAD3 exomes AF: 0.00863 AC: 2170AN: 251332Hom.: 15 AF XY: 0.00869 AC XY: 1180AN XY: 135828
GnomAD4 exome AF: 0.00833 AC: 12177AN: 1461876Hom.: 66 Cov.: 30 AF XY: 0.00841 AC XY: 6116AN XY: 727236
GnomAD4 genome ? AF: 0.00701 AC: 1068AN: 152256Hom.: 5 Cov.: 31 AF XY: 0.00708 AC XY: 527AN XY: 74440
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ZFYVE26: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 28, 2018 | - - |
Hereditary spastic paraplegia 15 Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 08, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 21, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at