14-67762309-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_015346.4(ZFYVE26):c.6263G>A(p.Arg2088His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2088C) has been classified as Uncertain significance.
Frequency
Consequence
NM_015346.4 missense
Scores
Clinical Significance
Conservation
Publications
- hereditary spastic paraplegia 15Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, G2P
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.6263G>A | p.Arg2088His | missense_variant | Exon 34 of 42 | ENST00000347230.9 | NP_056161.2 | |
ZFYVE26 | XM_047431173.1 | c.6263G>A | p.Arg2088His | missense_variant | Exon 34 of 42 | XP_047287129.1 | ||
ZFYVE26 | XM_047431174.1 | c.3938G>A | p.Arg1313His | missense_variant | Exon 23 of 31 | XP_047287130.1 | ||
ZFYVE26 | XM_047431175.1 | c.3845G>A | p.Arg1282His | missense_variant | Exon 23 of 31 | XP_047287131.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152146Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251238 AF XY: 0.00000736 show subpopulations
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727246 show subpopulations
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308 show subpopulations
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2088 of the ZFYVE26 protein (p.Arg2088His). This variant is present in population databases (rs769602785, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ZFYVE26-related conditions. ClinVar contains an entry for this variant (Variation ID: 583160). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at