Variant 6-17764665-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022113.6(KIF13A):c.4863C>G(p.Asp1621Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00834 in 1,613,880 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 70 hom. )

Consequence

KIF13A
NM_022113.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.278

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]

KIF13A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004205495).

BP6

Variant 6-17764665-G-C is Benign according to our data. Variant chr6-17764665-G-C is described in ClinVar as [Benign]. Clinvar id is 713152.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF13A	NM_022113.6 linkuse as main transcript	c.4863C>G	p.Asp1621Glu	missense_variant	39/39	ENST00000259711.11	NP_071396.4	Q9H1H9-1
KIF13A	NM_001105566.3 linkuse as main transcript	c.4758C>G	p.Asp1586Glu	missense_variant	38/38		NP_001099036.1	Q9H1H9-2
KIF13A	NM_001105567.3 linkuse as main transcript	c.4719C>G	p.Asp1573Glu	missense_variant	37/37		NP_001099037.1	Q9H1H9-4
KIF13A	NM_001105568.4 linkuse as main transcript	c.4719C>G	p.Asp1573Glu	missense_variant	37/38		NP_001099038.1	Q9H1H9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF13A	ENST00000259711.11 linkuse as main transcript	c.4863C>G	p.Asp1621Glu	missense_variant	39/39	1	NM_022113.6	ENSP00000259711.6		Q9H1H9-1

Frequencies

GnomAD3 genomes

AF:

0.00689

AC:

1049

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00615

AC:

1530

AN:

248832

Hom.:

AF XY:

0.00631

AC XY:

852

AN XY:

135000

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00375

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00661

GnomAD4 exome

AF:

0.00849

AC:

12410

AN:

1461616

Hom.:

Cov.:

AF XY:

0.00841

AC XY:

6114

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00148

Gnomad4 FIN exome

AF:

0.00240

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00797

GnomAD4 genome

AF:

0.00686

AC:

1045

AN:

152264

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

486

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00965

Hom.:

Bravo

AF:

0.00747

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00170

AC:

ESP6500EA

AF:

0.0106

AC:

ExAC

AF:

0.00664

AC:

803

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

.;T;T;.;.;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.87

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

D;D;D;D;D;D

MetaRNN

Benign

0.0042

T;T;T;T;T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

2.0

.;.;M;.;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

N;N;N;N;N;.

REVEL

Uncertain

0.37

Sift

Benign

0.033

D;D;D;D;D;.

Sift4G

Benign

0.25

T;D;T;T;T;.

Polyphen

1.0

D;.;D;D;D;.

Vest4

0.70

MutPred

0.11

.;.;Loss of loop (P = 0.0804);.;.;.;

MVP

0.60

MPC

0.84

ClinPred

0.029

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over