14-67798195-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_015346.4(ZFYVE26):c.2067C>T(p.Leu689=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,614,190 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L689L) has been classified as Likely benign.
Frequency
Consequence
NM_015346.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.2067C>T | p.Leu689= | synonymous_variant | 11/42 | ENST00000347230.9 | |
ZFYVE26 | XM_047431173.1 | c.2067C>T | p.Leu689= | synonymous_variant | 11/42 | ||
ZFYVE26 | XM_011536609.3 | c.2067C>T | p.Leu689= | synonymous_variant | 11/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.2067C>T | p.Leu689= | synonymous_variant | 11/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00166 AC: 253AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00233 AC: 585AN: 251468Hom.: 3 AF XY: 0.00252 AC XY: 342AN XY: 135912
GnomAD4 exome AF: 0.00220 AC: 3222AN: 1461886Hom.: 14 Cov.: 39 AF XY: 0.00223 AC XY: 1621AN XY: 727240
GnomAD4 genome AF: 0.00165 AC: 251AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.00161 AC XY: 120AN XY: 74474
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | ZFYVE26: BP4, BP7, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 30, 2018 | - - |
Hereditary spastic paraplegia 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 24, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at