rs76375909
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_015915.5(ATL1):āc.408T>Cā(p.Asp136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 1,613,430 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00053 ( 0 hom., cov: 32)
Exomes š: 0.00042 ( 3 hom. )
Consequence
ATL1
NM_015915.5 synonymous
NM_015915.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.701
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 14-50591066-T-C is Benign according to our data. Variant chr14-50591066-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 313293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.701 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000525 (80/152340) while in subpopulation EAS AF= 0.0143 (74/5188). AF 95% confidence interval is 0.0116. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATL1 | NM_015915.5 | c.408T>C | p.Asp136= | synonymous_variant | 3/14 | ENST00000358385.12 | |
ATL1 | NM_001127713.1 | c.408T>C | p.Asp136= | synonymous_variant | 4/14 | ||
ATL1 | NM_181598.4 | c.408T>C | p.Asp136= | synonymous_variant | 3/13 | ||
ATL1 | XM_047431430.1 | c.408T>C | p.Asp136= | synonymous_variant | 4/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATL1 | ENST00000358385.12 | c.408T>C | p.Asp136= | synonymous_variant | 3/14 | 1 | NM_015915.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000526 AC: 80AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00110 AC: 275AN: 250694Hom.: 2 AF XY: 0.00105 AC XY: 142AN XY: 135514
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GnomAD4 exome AF: 0.000416 AC: 608AN: 1461090Hom.: 3 Cov.: 32 AF XY: 0.000403 AC XY: 293AN XY: 726842
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
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 | Invitae | Dec 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, 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 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. - |
ATL1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 29, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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 12, 2016 | - - |
Hereditary spastic paraplegia 3A;C3150972:Neuropathy, hereditary sensory, type 1D Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 02, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at