rs750522064
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015346.4(ZFYVE26):c.273+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,610,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015346.4 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.273+8G>A | splice_region_variant, intron_variant | ENST00000347230.9 | |||
ZFYVE26 | XM_011536609.3 | c.273+8G>A | splice_region_variant, intron_variant | ||||
ZFYVE26 | XM_047431173.1 | c.273+8G>A | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.273+8G>A | splice_region_variant, intron_variant | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250354Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135328
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1458030Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 725518
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 15 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | The ZFYVE26 c.273+8G>A splice region variant has been reported in one study in which it is found in a homozygous state in one individual with autosomal recessive spastic paraplegia (Yoon et al. 2013). Control data are unavailable for this variant, which is reported at a frequency of 0.00071 in the East Asian population of the Exome Aggregation Consortium. The evidence for this variant is limited. The c.273+8G>A variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive spastic paraplegia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 17, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 03, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at