6-17794263-G-T

Variant names:

• chr6-17794263-G-T
• rs3734234
• NM_022113.6:c.3208C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022113.6(KIF13A):​c.3208C>A​(p.Leu1070Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIF13A NM_022113.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28736138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF13A	NM_022113.6	c.3208C>A	p.Leu1070Met	missense_variant	Exon 25 of 39	ENST00000259711.11	NP_071396.4
KIF13A	NM_001105566.3	c.3208C>A	p.Leu1070Met	missense_variant	Exon 25 of 38		NP_001099036.1
KIF13A	NM_001105567.3	c.3208C>A	p.Leu1070Met	missense_variant	Exon 25 of 37		NP_001099037.1
KIF13A	NM_001105568.4	c.3208C>A	p.Leu1070Met	missense_variant	Exon 25 of 38		NP_001099038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF13A	ENST00000259711.11	c.3208C>A	p.Leu1070Met	missense_variant	Exon 25 of 39	1	NM_022113.6	ENSP00000259711.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460350 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726402

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: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	.;T;T;.;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;T;D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.9	L;.;L;L;L;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.58	N;N;N;N;N;.
REVEL	Benign	0.21
Sift	Benign	0.50	T;T;D;T;D;.
Sift4G	Benign	0.58	T;T;D;T;D;.
Polyphen		0.27	B;.;B;D;D;.
Vest4		0.43
MutPred		0.23		Gain of MoRF binding (P = 0.0701);.;Gain of MoRF binding (P = 0.0701);Gain of MoRF binding (P = 0.0701);Gain of MoRF binding (P = 0.0701);.;
MVP		0.59
MPC		0.86
ClinPred		0.82	D
GERP RS		3.6
Varity_R		0.14
gMVP		0.32

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

Other links and lift over

dbSNP: rs3734234; hg19: chr6-17794494;