rs184939069

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001244008.2(KIF1A):ā€‹c.4971C>Gā€‹(p.Asp1657Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,610,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

KIF1A
NM_001244008.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0320
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KIF1A. . Gene score misZ 5.1579 (greater than the threshold 3.09). Trascript score misZ 5.0191 (greater than threshold 3.09). GenCC has associacion of gene with neuropathy, hereditary sensory, type 2C, hereditary spastic paraplegia 30, syndromic intellectual disability, intellectual disability, autosomal dominant 9, PEHO syndrome, autosomal dominant non-syndromic intellectual disability, hereditary sensory and autonomic neuropathy type 2.
BP4
Computational evidence support a benign effect (MetaRNN=0.07427797).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF1ANM_001244008.2 linkuse as main transcriptc.4971C>G p.Asp1657Glu missense_variant 46/49 ENST00000498729.9 NP_001230937.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF1AENST00000498729.9 linkuse as main transcriptc.4971C>G p.Asp1657Glu missense_variant 46/495 NM_001244008.2 ENSP00000438388 Q12756-3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
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:
0.00000410
AC:
1
AN:
244126
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132994
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000910
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458364
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
725320
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152362
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000829
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
14
DANN
Benign
0.42
DEOGEN2
Benign
0.088
T;.;.;.;.;.;.;T;.;.;.;.;.;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.75
.;T;T;T;T;T;.;T;T;T;T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.074
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.68
N;.;.;.;.;.;.;N;.;.;.;.;.;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.24
.;N;.;.;.;.;.;.;.;.;.;.;.;.
REVEL
Benign
0.037
Sift
Benign
0.59
.;T;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G
Benign
0.83
.;T;.;.;.;.;.;.;.;.;.;.;.;.
Polyphen
0.0
B;.;.;.;.;.;.;B;.;.;.;.;.;.
Vest4
0.060
MutPred
0.20
Gain of loop (P = 0.1069);.;.;.;.;.;.;Gain of loop (P = 0.1069);.;.;.;.;.;.;
MVP
0.21
MPC
0.40
ClinPred
0.018
T
GERP RS
2.1
Varity_R
0.046
gMVP
0.11

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: rs184939069; hg19: chr2-241659241; API