Variant 1-245367144-G-T 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_018012.4(KIF26B):c.776G>T(p.Gly259Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000745 in 1,601,854 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00050 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 13 hom. )

Consequence

KIF26B
NM_018012.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

KIF26B (HGNC:25484): (kinesin family member 26B) The protein encoded by this gene is an intracellular motor protein thought to transport organelles along microtubules. The encoded protein is required for kidney development. Elevated levels of this protein have been found in some breast and colorectal cancers. [provided by RefSeq, Mar 2017]

KIF26B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055597723).

BP6

Variant 1-245367144-G-T is Benign according to our data. Variant chr1-245367144-G-T is described in ClinVar as [Benign]. Clinvar id is 3048017.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF26B	NM_018012.4 linkuse as main transcript	c.776G>T	p.Gly259Val	missense_variant	3/15	ENST00000407071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF26B	ENST00000407071.7 linkuse as main transcript	c.776G>T	p.Gly259Val	missense_variant	3/15	1	NM_018012.4	A2	Q2KJY2-1
KIF26B	ENST00000479506.1 linkuse as main transcript	n.550G>T		non_coding_transcript_exon_variant	2/4	1

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00160

AC:

363

AN:

226496

Hom.:

AF XY:

0.00211

AC XY:

259

AN XY:

122522

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000681

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000548

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000297

Gnomad OTH exome

AF:

0.000710

GnomAD4 exome

AF:

0.000771

AC:

1117

AN:

1449502

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

799

AN XY:

719760

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.000744

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000333

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.000650

GnomAD4 genome

AF:

0.000499

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000711

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000117

ExAC

AF:

0.00160

AC:

193

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KIF26B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.081

Eigen

Benign

-0.017

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

REVEL

Benign

0.21

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.035

Polyphen

0.10

Vest4

0.35

MVP

0.34

MPC

0.38

ClinPred

0.057

GERP RS

4.5

Varity_R

0.19

gMVP

0.33

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