NM_015656.2:c.25T>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C9G) has been classified 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

Publications

1 publications found

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:

KIF26A-DT (HGNC:55439): (KIF26A divergent transcript)

KIF26A-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

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

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0006 (91/151692) while in subpopulation AMR AF = 0.00491 (75/15260). AF 95% confidence interval is 0.00402. There are 1 homozygotes in GnomAd4. There are 42 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015656.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF26A	NM_015656.2	MANE Select	c.25T>C	p.Cys9Arg	missense	Exon 1 of 15	NP_056471.1	Q9ULI4
	KIF26A-DT	NR_158217.1		n.-118A>G		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF26A	ENST00000423312.7	TSL:5 MANE Select	c.25T>C	p.Cys9Arg	missense	Exon 1 of 15	ENSP00000388241.2	Q9ULI4
KIF26A	ENST00000926957.1		c.25T>C	p.Cys9Arg	missense	Exon 1 of 15	ENSP00000597016.1
KIF26A	ENST00000697132.1		c.139-296T>C		intron	N/A	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

GnomAD2 exomes

AF:

0.00

AC:

AN:

2046

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

146

AN:

1111686

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

530150

show subpopulations

African (AFR)

AF:

0.0000439

AC:

AN:

22782

American (AMR)

AF:

0.0100

AC:

AN:

8500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14698

East Asian (EAS)

AF:

0.00133

AC:

AN:

26276

South Asian (SAS)

AF:

0.00

AC:

AN:

29082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3012

European-Non Finnish (NFE)

AF:

0.00000639

AC:

AN:

939062

Other (OTH)

AF:

0.000425

AC:

AN:

44748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000600

AC:

AN:

151692

Hom.:

Cov.:

AF XY:

0.000566

AC XY:

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.000266

AC:

AN:

41422

American (AMR)

AF:

0.00491

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000393

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67856

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00127

Asia WGS

AF:

0.000580

AC:

AN:

3462

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

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

PhyloP100

-0.022

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

PromoterAI

0.051

Neutral

(source)

Varity_R

0.64

gMVP

0.39

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over