rs192133963

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022113.6(KIF13A):c.3280G>C(p.Val1094Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,609,924 control chromosomes in the GnomAD database, including 21 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 9 hom. )

Consequence

KIF13A
NM_022113.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006504804).

BP6

Variant 6-17787857-C-G is Benign according to our data. Variant chr6-17787857-C-G is described in ClinVar as [Benign]. Clinvar id is 792034.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00595 (906/152300) while in subpopulation AFR AF = 0.02 (832/41566). AF 95% confidence interval is 0.0189. There are 12 homozygotes in GnomAd4. There are 398 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF13A	NM_022113.6 link	c.3280G>C	p.Val1094Leu	missense_variant	Exon 27 of 39	ENST00000259711.11	NP_071396.4	Q9H1H9-1
KIF13A	NM_001105566.3 link	c.3280G>C	p.Val1094Leu	missense_variant	Exon 27 of 38		NP_001099036.1	Q9H1H9-2
KIF13A	NM_001105567.3 link	c.3241G>C	p.Val1081Leu	missense_variant	Exon 26 of 37		NP_001099037.1	Q9H1H9-4
KIF13A	NM_001105568.4 link	c.3241G>C	p.Val1081Leu	missense_variant	Exon 26 of 38		NP_001099038.1	Q9H1H9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF13A	ENST00000259711.11 link	c.3280G>C	p.Val1094Leu	missense_variant	Exon 27 of 39	1	NM_022113.6	ENSP00000259711.6		Q9H1H9-1

Frequencies

GnomAD3 genomes

AF:

0.00597

AC:

908

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00140

AC:

349

AN:

249180

AF XY:

0.00105

show subpopulations

Gnomad AFR exome

AF:

0.0186

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000688

AC:

1003

AN:

1457624

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

446

AN XY:

725528

show subpopulations

African (AFR)

AF:

0.0181

AC:

604

AN:

33386

American (AMR)

AF:

0.00136

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000227

AC:

252

AN:

1108206

Other (OTH)

AF:

0.00130

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00595

AC:

906

AN:

152300

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

398

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0200

AC:

832

AN:

41566

American (AMR)

AF:

0.00333

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68028

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

130

173

216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000258

Hom.:

Bravo

AF:

0.00646

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0174

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.00175

AC:

211

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.011

.;T;T;.;.;T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D;D;D;D;D;D

MetaRNN

Benign

0.0065

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.53

.;.;N;.;N;.;.

PhyloP100

1.5

PrimateAI

Uncertain

0.69

PROVEAN

Benign

1.0

N;N;N;N;N;.;N

REVEL

Benign

0.054

Sift

Benign

1.0

T;T;T;T;T;.;T

Sift4G

Benign

1.0

T;T;T;T;T;.;T

Polyphen

0.016

B;.;B;B;B;.;.

Vest4

0.33

MutPred

0.28

.;.;Gain of catalytic residue at V1094 (P = 0.0203);.;Gain of catalytic residue at V1094 (P = 0.0203);.;.;

MVP

0.33

MPC

0.27

ClinPred

0.014

GERP RS

5.0

Varity_R

0.025

gMVP

0.34

Mutation Taster

=100/0

polymorphism

(source)

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 for variant 6:17787857 C>G . It may be empty.

rs192133963

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over