rs771217469
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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.4638C>T(p.Asn1546=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,547,304 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 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
KIF1A
NM_001244008.2 synonymous
NM_001244008.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.959
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=-0.72).
BP6
?
Variant 2-240722483-G-A is Benign according to our data. Variant chr2-240722483-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211289.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr2-240722483-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.959 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000105 (147/1395060) while in subpopulation SAS AF= 0.000607 (48/79138). AF 95% confidence interval is 0.000469. There are 0 homozygotes in gnomad4_exome. There are 84 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.4638C>T | p.Asn1546= | synonymous_variant | 43/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.4638C>T | p.Asn1546= | synonymous_variant | 43/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152128Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000871 AC: 13AN: 149308Hom.: 0 AF XY: 0.0000999 AC XY: 8AN XY: 80050
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GnomAD4 exome AF: 0.000105 AC: 147AN: 1395060Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 84AN XY: 688084
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74416
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 19, 2015 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | 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. - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Oct 02, 2017 | - - |
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 27, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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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