6-17764819-A-G

Position:

• chr6-17764819-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022113.6(KIF13A):​c.4709T>C​(p.Phe1570Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: 32)
• Consequence: KIF13A NM_022113.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76

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]

ACMG classification

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=0.08431846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF13A	NM_022113.6	c.4709T>C	p.Phe1570Ser	missense_variant	39/39	ENST00000259711.11	NP_071396.4
KIF13A	NM_001105566.3	c.4604T>C	p.Phe1535Ser	missense_variant	38/38		NP_001099036.1
KIF13A	NM_001105567.3	c.4565T>C	p.Phe1522Ser	missense_variant	37/37		NP_001099037.1
KIF13A	NM_001105568.4	c.4565T>C	p.Phe1522Ser	missense_variant	37/38		NP_001099038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF13A	ENST00000259711.11	c.4709T>C	p.Phe1570Ser	missense_variant	39/39	1	NM_022113.6	ENSP00000259711.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.4709T>C (p.F1570S) alteration is located in exon 39 (coding exon 39) of the KIF13A gene. This alteration results from a T to C substitution at nucleotide position 4709, causing the phenylalanine (F) at amino acid position 1570 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0097	.;T;T;.;.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.73	T;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.084	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	.;.;N;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.080	N;N;N;N;N;.
REVEL	Benign	0.095
Sift	Benign	0.34	T;T;T;T;T;.
Sift4G	Benign	0.46	T;T;T;T;T;.
Polyphen		0.0	B;.;B;B;B;.
Vest4		0.20
MutPred		0.50		.;.;Gain of disorder (P = 0.0067);.;.;.;
MVP		0.15
MPC		0.42
ClinPred		0.44	T
GERP RS		4.9
Varity_R		0.049
gMVP		0.37

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: chr6-17765050;