Variant 14-104138747-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015656.2(KIF26A):c.25T>C(p.Cys9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,263,378 control chromosomes in the GnomAD database, including 2 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

KIF26A
NM_015656.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0220

Variant links:

Genes affected

KIF26A (HGNC:20226): (kinesin family member 26A) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in enteric nervous system development; negative regulation of signal transduction; and regulation of cell growth by extracellular stimulus. Predicted to be located in cytosol. Predicted to be part of kinesin complex. Predicted to be active in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

KIF26A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025992066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF26A	NM_015656.2 linkuse as main transcript	c.25T>C	p.Cys9Arg	missense_variant	1/15	ENST00000423312.7	NP_056471.1	Q9ULI4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF26A	ENST00000423312.7 linkuse as main transcript	c.25T>C	p.Cys9Arg	missense_variant	1/15	5	NM_015656.2	ENSP00000388241.2		Q9ULI4
KIF26A	ENST00000697132.1 linkuse as main transcript	c.139-296T>C		intron_variant				ENSP00000513129.1		A0A8V8TM02

Frequencies

GnomAD3 genomes

AF:

0.000600

AC:

AN:

151584

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00492

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000959

GnomAD4 exome

AF:

0.000131

AC:

146

AN:

1111686

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

530150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000439

Gnomad4 AMR exome

AF:

0.0100

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00133

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000639

Gnomad4 OTH exome

AF:

0.000425

GnomAD4 genome

AF:

0.000600

AC:

AN:

151692

Hom.:

Cov.:

AF XY:

0.000566

AC XY:

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000393

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000949

Bravo

AF:

0.00127

Asia WGS

AF:

0.000580

AC:

AN:

3462

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

Jul 09, 2021

The c.25T>C (p.C9R) alteration is located in exon 1 (coding exon 1) of the KIF26A gene. This alteration results from a T to C substitution at nucleotide position 25, causing the cysteine (C) at amino acid position 9 to be replaced by an arginine (R). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.40

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.81

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.1

REVEL

Benign

0.084

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Polyphen

0.099

Vest4

0.23

MutPred

0.39

Gain of MoRF binding (P = 7e-04);

MVP

0.39

MPC

4.9

ClinPred

0.33

GERP RS

-1.1

Varity_R

0.64

gMVP

0.39

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