14-50587817-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_015915.5(ATL1):c.35-14G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,614,164 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0083 ( 15 hom., cov: 32)
Exomes 𝑓: 0.00079 ( 11 hom. )
Consequence
ATL1
NM_015915.5 splice_polypyrimidine_tract, intron
NM_015915.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.975
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 14-50587817-G-A is Benign according to our data. Variant chr14-50587817-G-A is described in ClinVar as [Benign]. Clinvar id is 516491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00834 (1271/152332) while in subpopulation AFR AF= 0.0287 (1192/41580). AF 95% confidence interval is 0.0273. There are 15 homozygotes in gnomad4. There are 617 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 15 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATL1 | NM_015915.5 | c.35-14G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000358385.12 | |||
ATL1 | NM_001127713.1 | c.35-14G>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
ATL1 | NM_181598.4 | c.35-14G>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
ATL1 | XM_047431430.1 | c.35-14G>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATL1 | ENST00000358385.12 | c.35-14G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_015915.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00834 AC: 1269AN: 152214Hom.: 15 Cov.: 32
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GnomAD3 exomes AF: 0.00219 AC: 550AN: 251250Hom.: 6 AF XY: 0.00152 AC XY: 207AN XY: 135828
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GnomAD4 exome AF: 0.000788 AC: 1152AN: 1461832Hom.: 11 Cov.: 31 AF XY: 0.000624 AC XY: 454AN XY: 727218
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 3A Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 07, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Neuropathy, hereditary sensory, type 1D Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Computational scores
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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