rs151344519
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3PP5
The NM_006796.3(AFG3L2):c.2021_2022delinsTA(p.Ser674Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
AFG3L2
NM_006796.3 missense
NM_006796.3 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.56
Genes affected
AFG3L2 (HGNC:315): (AFG3 like matrix AAA peptidase subunit 2) This gene encodes a protein localized in mitochondria and closely related to paraplegin. The paraplegin gene is responsible for an autosomal recessive form of hereditary spastic paraplegia. This gene is a candidate gene for other hereditary spastic paraplegias or neurodegenerative disorders. [provided by RefSeq, Jul 2008]
TUBB6 (HGNC:20776): (tubulin beta 6 class V) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 5 uncertain in NM_006796.3
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 18-12337494-GG-TA is Pathogenic according to our data. Variant chr18-12337494-GG-TA is described in ClinVar as [Pathogenic]. Clinvar id is 5471.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AFG3L2 | NM_006796.3 | c.2021_2022delinsTA | p.Ser674Leu | missense_variant | 16/17 | ENST00000269143.8 | |
LOC107985154 | XR_002958227.2 | n.3291+592_3291+593delinsTA | intron_variant, non_coding_transcript_variant | ||||
AFG3L2 | XM_011525601.4 | c.1820_1821delinsTA | p.Ser607Leu | missense_variant | 15/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFG3L2 | ENST00000269143.8 | c.2021_2022delinsTA | p.Ser674Leu | missense_variant | 16/17 | 1 | NM_006796.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spinocerebellar ataxia type 28 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at