rs373045276

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_001244008.2(KIF1A):​c.3132C>T​(p.Ile1044Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 1,582,944 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 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

KIF1A
NM_001244008.2 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -2.94
Variant links:
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 2-240746109-G-A is Benign according to our data. Variant chr2-240746109-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 789409.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-2.94 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF1ANM_001244008.2 linkuse as main transcriptc.3132C>T p.Ile1044Ile synonymous_variant 30/49 ENST00000498729.9 NP_001230937.1 Q12756-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF1AENST00000498729.9 linkuse as main transcriptc.3132C>T p.Ile1044Ile synonymous_variant 30/495 NM_001244008.2 ENSP00000438388.1 Q12756-3

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152208
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000204
AC:
4
AN:
195950
Hom.:
0
AF XY:
0.00000944
AC XY:
1
AN XY:
105938
show subpopulations
Gnomad AFR exome
AF:
0.000279
Gnomad AMR exome
AF:
0.0000346
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000126
AC:
18
AN:
1430736
Hom.:
0
Cov.:
33
AF XY:
0.0000113
AC XY:
8
AN XY:
708930
show subpopulations
Gnomad4 AFR exome
AF:
0.000335
Gnomad4 AMR exome
AF:
0.0000249
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000526
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000273
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152208
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.000434
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000147

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenNov 01, 2018- -
Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 07, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
0.96
DANN
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373045276; hg19: chr2-241685526; COSMIC: COSV105204646; COSMIC: COSV105204646; API