6-17764207-G-A

Variant summary

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

The NM_022113.6(KIF13A):​c.5321C>T​(p.Ser1774Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,710 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

KIF13A
NM_022113.6 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10
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=0.11837053).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF13ANM_022113.6 linkuse as main transcriptc.5321C>T p.Ser1774Phe missense_variant 39/39 ENST00000259711.11 NP_071396.4 Q9H1H9-1
KIF13ANM_001105566.3 linkuse as main transcriptc.5216C>T p.Ser1739Phe missense_variant 38/38 NP_001099036.1 Q9H1H9-2
KIF13ANM_001105567.3 linkuse as main transcriptc.5177C>T p.Ser1726Phe missense_variant 37/37 NP_001099037.1 Q9H1H9-4
KIF13ANM_001105568.4 linkuse as main transcriptc.5177C>T p.Ser1726Phe 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.5321C>T p.Ser1774Phe missense_variant 39/391 NM_022113.6 ENSP00000259711.6 Q9H1H9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461710
Hom.:
0
Cov.:
34
AF XY:
0.00000825
AC XY:
6
AN XY:
727138
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:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsApr 18, 2023The c.5321C>T (p.S1774F) alteration is located in exon 39 (coding exon 39) of the KIF13A gene. This alteration results from a C to T substitution at nucleotide position 5321, causing the serine (S) at amino acid position 1774 to be replaced by a phenylalanine (F). 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
0.11
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
.;T;T;.;.;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.85
T;T;T;T;T;T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.12
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
.;.;N;.;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.4
N;N;N;N;N;.
REVEL
Benign
0.073
Sift
Uncertain
0.026
D;D;D;D;D;.
Sift4G
Uncertain
0.045
D;T;D;D;D;.
Polyphen
0.12
B;.;B;B;B;.
Vest4
0.22
MutPred
0.23
.;.;Loss of disorder (P = 0.0174);.;.;.;
MVP
0.30
MPC
0.34
ClinPred
0.30
T
GERP RS
5.8
Varity_R
0.029
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-17764438; API