Variant 1-245688693-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_018012.4(KIF26B):c.5710G>C(p.Asp1904His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,606,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1904N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

KIF26B
NM_018012.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.79

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:

LOC105373265 (HGNC:):

LOC105373265 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.831

BS2

High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF26B	NM_018012.4 linkuse as main transcript	c.5710G>C	p.Asp1904His	missense_variant	12/15	ENST00000407071.7	NP_060482.2	Q2KJY2-1
LOC105373265	XR_007066988.1 linkuse as main transcript	n.657-4242C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF26B	ENST00000407071.7 linkuse as main transcript	c.5710G>C	p.Asp1904His	missense_variant	12/15	1	NM_018012.4	ENSP00000385545.2		Q2KJY2-1
KIF26B	ENST00000366518.4 linkuse as main transcript	c.4567G>C	p.Asp1523His	missense_variant	9/12	5		ENSP00000355475.4		B7WPD9

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000162

AC:

AN:

222636

Hom.:

AF XY:

0.000146

AC XY:

AN XY:

123444

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000120

Gnomad ASJ exome

AF:

0.000214

Gnomad EAS exome

AF:

0.000412

Gnomad SAS exome

AF:

0.000173

Gnomad FIN exome

AF:

0.000202

Gnomad NFE exome

AF:

0.0000931

Gnomad OTH exome

AF:

0.000362

GnomAD4 exome

AF:

0.000102

AC:

148

AN:

1454376

Hom.:

Cov.:

AF XY:

0.0000899

AC XY:

AN XY:

723024

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0000904

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.000304

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.000216

Gnomad4 NFE exome

AF:

0.0000874

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.000164

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.000144

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

D;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Pathogenic

0.81

MutationAssessor

Pathogenic

3.2

M;.

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-6.5

D;D

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.90

MVP

0.88

MPC

0.36

ClinPred

0.24

GERP RS

5.3

Varity_R

0.76

gMVP

0.73

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over