chr14-50590980-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 5P and 6B. PM1PM2PP2BP4BP6BS1
The NM_015915.5(ATL1):āc.322A>Gā(p.Thr108Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000103 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015915.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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ATL1 | NM_015915.5 | c.322A>G | p.Thr108Ala | missense_variant | Exon 3 of 14 | ENST00000358385.12 | NP_056999.2 | |
ATL1 | NM_001127713.1 | c.322A>G | p.Thr108Ala | missense_variant | Exon 4 of 14 | NP_001121185.1 | ||
ATL1 | NM_181598.4 | c.322A>G | p.Thr108Ala | missense_variant | Exon 3 of 13 | NP_853629.2 | ||
ATL1 | XM_047431430.1 | c.322A>G | p.Thr108Ala | missense_variant | Exon 4 of 15 | XP_047287386.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000163 AC: 41AN: 251250Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135794
GnomAD4 exome AF: 0.000103 AC: 151AN: 1461626Hom.: 0 Cov.: 30 AF XY: 0.000100 AC XY: 73AN XY: 727118
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23334294) -
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Hereditary spastic paraplegia 3A Benign:2
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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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Inborn genetic diseases Uncertain:1
The p.T108A variant (also known as c.322A>G), located in coding exon 3 of the ATL1 gene, results from an A to G substitution at nucleotide position 322. The threonine at codon 108 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant spastic paraplegia 3A or hereditary sensory neuropathy type ID; however, its contribution to the development of autosomal recessive spastic paraplegia 3A is uncertain. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at