6-17764765-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022113.6(KIF13A):​c.4763G>A​(p.Arg1588His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,612,958 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

KIF13A
NM_022113.6 missense

Scores

4
3
12

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21896988).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF13ANM_022113.6 linkuse as main transcriptc.4763G>A p.Arg1588His missense_variant 39/39 ENST00000259711.11 NP_071396.4 Q9H1H9-1
KIF13ANM_001105566.3 linkuse as main transcriptc.4658G>A p.Arg1553His missense_variant 38/38 NP_001099036.1 Q9H1H9-2
KIF13ANM_001105567.3 linkuse as main transcriptc.4619G>A p.Arg1540His missense_variant 37/37 NP_001099037.1 Q9H1H9-4
KIF13ANM_001105568.4 linkuse as main transcriptc.4619G>A p.Arg1540His 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.4763G>A p.Arg1588His missense_variant 39/391 NM_022113.6 ENSP00000259711.6 Q9H1H9-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152064
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000445
AC:
11
AN:
246966
Hom.:
0
AF XY:
0.0000448
AC XY:
6
AN XY:
133966
show subpopulations
Gnomad AFR exome
AF:
0.0000655
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000560
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000715
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000746
AC:
109
AN:
1460776
Hom.:
0
Cov.:
34
AF XY:
0.0000661
AC XY:
48
AN XY:
726582
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000449
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000873
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000948
Hom.:
0
Bravo
AF:
0.000178
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.000250
AC:
1
ESP6500EA
AF:
0.000360
AC:
3
ExAC
AF:
0.0000662
AC:
8

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 02, 2022The c.4763G>A (p.R1588H) 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 4763, causing the arginine (R) at amino acid position 1588 to be replaced by a histidine (H). 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
Benign
0.15
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.058
.;T;T;.;.;T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.22
T;T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
2.0
.;.;M;.;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.92
N;N;N;N;N;.
REVEL
Benign
0.25
Sift
Benign
0.053
T;D;D;D;D;.
Sift4G
Benign
0.13
T;T;T;T;T;.
Polyphen
1.0
D;.;D;D;D;.
Vest4
0.57
MVP
0.73
MPC
0.92
ClinPred
0.41
T
GERP RS
6.1
Varity_R
0.059
gMVP
0.41

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: rs184686655; hg19: chr6-17764996; COSMIC: COSV52451260; API