Variant 8-29070658-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015254.4(KIF13B):c.5327G>C(p.Arg1776Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000206 in 1,562,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

KIF13B
NM_015254.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Variant links:

Genes affected

KIF13B (HGNC:14405): (kinesin family member 13B) Enables 14-3-3 protein binding activity and protein kinase binding activity. Involved in regulation of axonogenesis. Located in axon and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

KIF13B links:

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=0.21875307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF13B	NM_015254.4 linkuse as main transcript	c.5327G>C	p.Arg1776Pro	missense_variant	40/40	ENST00000524189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF13B	ENST00000524189.6 linkuse as main transcript	c.5327G>C	p.Arg1776Pro	missense_variant	40/40	1	NM_015254.4	P1	Q9NQT8-1
KIF13B	ENST00000523130.1 linkuse as main transcript	c.1103G>C	p.Arg368Pro	missense_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000172

AC:

AN:

162408

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

88248

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000777

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.000669

GnomAD4 exome

AF:

0.000206

AC:

290

AN:

1410706

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

148

AN XY:

697374

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.000108

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:

0.000250

Gnomad4 OTH exome

AF:

0.000171

GnomAD4 genome

AF:

0.000210

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000219

ExAC

AF:

0.000166

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Nov 21, 2022

The c.5327G>C (p.R1776P) alteration is located in exon 40 (coding exon 40) of the KIF13B gene. This alteration results from a G to C substitution at nucleotide position 5327, causing the arginine (R) at amino acid position 1776 to be replaced by a proline (P). 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

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.14

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.12

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

T;T

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.1

N;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.011

D;D

Vest4

0.34

MVP

0.81

MPC

0.41

ClinPred

0.27

GERP RS

4.5

Varity_R

0.24

gMVP

0.66

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