rs200310890
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2
The NM_015915.5(ATL1):c.417+3A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,612,848 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 82 hom. )
Consequence
ATL1
NM_015915.5 splice_donor_region, intron
NM_015915.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9970
2
Clinical Significance
Conservation
PhyloP100: 2.86
Genes affected
ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 14-50591078-A-G is Benign according to our data. Variant chr14-50591078-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 313294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-50591078-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00112 (170/152332) while in subpopulation SAS AF= 0.0328 (158/4824). AF 95% confidence interval is 0.0286. There are 2 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 3 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATL1 | NM_015915.5 | c.417+3A>G | splice_donor_region_variant, intron_variant | ENST00000358385.12 | |||
ATL1 | NM_001127713.1 | c.417+3A>G | splice_donor_region_variant, intron_variant | ||||
ATL1 | NM_181598.4 | c.417+3A>G | splice_donor_region_variant, intron_variant | ||||
ATL1 | XM_047431430.1 | c.417+3A>G | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATL1 | ENST00000358385.12 | c.417+3A>G | splice_donor_region_variant, intron_variant | 1 | NM_015915.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00113 AC: 172AN: 152214Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00436 AC: 1091AN: 250326Hom.: 41 AF XY: 0.00566 AC XY: 766AN XY: 135350
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GnomAD4 exome AF: 0.00202 AC: 2946AN: 1460516Hom.: 82 Cov.: 32 AF XY: 0.00285 AC XY: 2071AN XY: 726566
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 3A Benign:3
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | ATL1: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2019 | This variant is associated with the following publications: (PMID: 30919572) - |
Neuropathy, hereditary sensory, type 1D Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 16, 2021 | - - |
Hereditary spastic paraplegia 3A;C3150972:Neuropathy, hereditary sensory, type 1D Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 16, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Benign
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -11
Find out detailed SpliceAI scores and Pangolin per-transcript scores at