2-240762747-G-T

Variant summary

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

The NM_001244008.2(KIF1A):​c.2088C>A​(p.Asn696Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KIF1A
NM_001244008.2 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.325
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the KIF1A gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 112 curated pathogenic missense variants (we use a threshold of 10). The gene has 150 curated benign missense variants. Gene score misZ: 5.1579 (above the threshold of 3.09). Trascript score misZ: 5.0191 (above the threshold of 3.09). GenCC associations: The gene is linked to 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=0.072675526).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF1ANM_001244008.2 linkc.2088C>A p.Asn696Lys missense_variant Exon 23 of 49 ENST00000498729.9 NP_001230937.1 Q12756-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF1AENST00000498729.9 linkc.2088C>A p.Asn696Lys missense_variant Exon 23 of 49 5 NM_001244008.2 ENSP00000438388.1 Q12756-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000412
AC:
1
AN:
242866
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
131780
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:
0.00000909
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1443806
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
714320
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000826
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
1.8
DANN
Benign
0.93
DEOGEN2
Benign
0.22
T;.;.;.;.;.;.;T;.;.;.;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.93
.;D;D;D;D;D;.;D;D;D;D;D;D
M_CAP
Uncertain
0.088
D
MetaRNN
Benign
0.073
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.4
L;.;.;.;.;.;.;L;.;.;.;.;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.7
.;N;N;.;.;.;.;.;.;.;.;.;N
REVEL
Benign
0.077
Sift
Benign
0.89
.;T;T;.;.;.;.;.;.;.;.;.;T
Sift4G
Benign
0.89
.;T;T;.;.;.;.;.;.;.;.;.;.
Polyphen
0.16
B;.;.;.;.;.;.;B;.;.;.;.;B
Vest4
0.41, 0.35
MutPred
0.35
Gain of ubiquitination at N687 (P = 0.0014);.;Gain of ubiquitination at N687 (P = 0.0014);.;.;Gain of ubiquitination at N687 (P = 0.0014);Gain of ubiquitination at N687 (P = 0.0014);Gain of ubiquitination at N687 (P = 0.0014);Gain of ubiquitination at N687 (P = 0.0014);.;Gain of ubiquitination at N687 (P = 0.0014);.;.;
MVP
0.71
MPC
0.55
ClinPred
0.085
T
GERP RS
-1.6
Varity_R
0.077
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs758111969; hg19: chr2-241702164; API