Genetic Variant NM_015656.2:c.20C>T (chr14-104138742-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BS1_Supporting

The NM_015656.2(KIF26A):c.20C>T(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,268,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

KIF26A
NM_015656.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Publications

0 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27037877).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000198 (3/151786) while in subpopulation EAS AF = 0.000582 (3/5152). AF 95% confidence interval is 0.000158. There are 0 homozygotes in GnomAd4. There are 0 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.20C>T	p.Pro7Leu	missense	Exon 1 of 15	NP_056471.1	Q9ULI4
	KIF26A-DT	NR_158217.1		n.-113G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF26A	ENST00000423312.7	TSL:5 MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 1 of 15	ENSP00000388241.2	Q9ULI4
KIF26A	ENST00000926957.1		c.20C>T	p.Pro7Leu	missense	Exon 1 of 15	ENSP00000597016.1
KIF26A	ENST00000697132.1		c.139-301C>T		intron	N/A	ENSP00000513129.1	A0A8V8TM02

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

2788

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:

0.0000125

AC:

AN:

1117190

Hom.:

Cov.:

AF XY:

0.0000150

AC XY:

AN XY:

534094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22786

American (AMR)

AF:

0.00

AC:

AN:

8722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14750

East Asian (EAS)

AF:

0.000153

AC:

AN:

26210

South Asian (SAS)

AF:

0.0000321

AC:

AN:

31176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3016

European-Non Finnish (NFE)

AF:

0.00000743

AC:

AN:

941814

Other (OTH)

AF:

0.0000446

AC:

AN:

44858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.0000198

AC:

AN:

151786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41400

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000582

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67902

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000416

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

Benign

0.24

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.55

PhyloP100

2.1

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.51

REVEL

Benign

0.20

Sift

Benign

0.037

Sift4G

Benign

0.51

Polyphen

0.77

Vest4

0.11

MutPred

0.29

Gain of MoRF binding (P = 0.0469)

MVP

0.64

MPC

2.0

ClinPred

0.21

GERP RS

2.2

PromoterAI

0.041

Neutral

(source)

Varity_R

0.052

gMVP

0.20

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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