rs202049905
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The NM_001244008.2(KIF1A):c.4851C>T(p.Tyr1617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,581,504 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
Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 0 hom. )
Consequence
KIF1A
NM_001244008.2 synonymous
NM_001244008.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.781
Genes affected
KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 2-240720931-G-A is Benign according to our data. Variant chr2-240720931-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 335257.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=4}.
BP7
?
Synonymous conserved (PhyloP=-0.781 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000269 (41/152308) while in subpopulation SAS AF= 0.00166 (8/4822). AF 95% confidence interval is 0.000825. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.4851C>T | p.Tyr1617= | synonymous_variant | 45/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.4851C>T | p.Tyr1617= | synonymous_variant | 45/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000403 AC: 81AN: 200984Hom.: 0 AF XY: 0.000423 AC XY: 46AN XY: 108692
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GnomAD4 exome AF: 0.000218 AC: 312AN: 1429196Hom.: 0 Cov.: 31 AF XY: 0.000271 AC XY: 192AN XY: 707464
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2022 | See Variant Classification Assertion Criteria. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2021 | - - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 01, 2018 | - - |
Hereditary spastic paraplegia 30 Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 14, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
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