6-17764735-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022113.6(KIF13A):​c.4793G>A​(p.Gly1598Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

KIF13A
NM_022113.6 missense

Scores

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
KIF13A (HGNC:14566): (kinesin family member 13A) This gene encodes a member of the kinesin family of microtubule-based motor proteins that function in the positioning of endosomes. This family member can direct mannose-6-phosphate receptor-containing vesicles from the trans-Golgi network to the plasma membrane, and it is necessary for the steady-state distribution of late endosomes/lysosomes. It is also required for the translocation of FYVE-CENT and TTC19 from the centrosome to the midbody during cytokinesis, and it plays a role in melanosome maturation. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF13ANM_022113.6 linkuse as main transcriptc.4793G>A p.Gly1598Asp missense_variant 39/39 ENST00000259711.11 NP_071396.4 Q9H1H9-1
KIF13ANM_001105566.3 linkuse as main transcriptc.4688G>A p.Gly1563Asp missense_variant 38/38 NP_001099036.1 Q9H1H9-2
KIF13ANM_001105567.3 linkuse as main transcriptc.4649G>A p.Gly1550Asp missense_variant 37/37 NP_001099037.1 Q9H1H9-4
KIF13ANM_001105568.4 linkuse as main transcriptc.4649G>A p.Gly1550Asp missense_variant 37/38 NP_001099038.1 Q9H1H9-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF13AENST00000259711.11 linkuse as main transcriptc.4793G>A p.Gly1598Asp missense_variant 39/391 NM_022113.6 ENSP00000259711.6 Q9H1H9-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152088
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00000809
AC:
2
AN:
247140
Hom.:
0
AF XY:
0.00000746
AC XY:
1
AN XY:
134036
show subpopulations
Gnomad AFR exome
AF:
0.000131
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152088
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
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
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 08, 2023The c.4793G>A (p.G1598D) alteration is located in exon 39 (coding exon 39) of the KIF13A gene. This alteration results from a G to A substitution at nucleotide position 4793, causing the glycine (G) at amino acid position 1598 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
.;T;T;.;.;T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.71
D;D;D;D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.6
.;.;L;.;.;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-4.8
D;D;D;D;D;.
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D;D;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;.
Polyphen
1.0
D;.;D;D;D;.
Vest4
0.76
MutPred
0.41
.;.;Gain of helix (P = 0.0496);.;.;.;
MVP
0.55
MPC
1.0
ClinPred
0.99
D
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.74
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs780359848; hg19: chr6-17764966; COSMIC: COSV52464596; API