NM_015656.2:c.25T>C

Variant summary

Our verdict is Likely benign. Variant got -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. 13/20 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

2
1
14

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

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF26ANM_015656.2 linkc.25T>C p.Cys9Arg missense_variant Exon 1 of 15 ENST00000423312.7 NP_056471.1 Q9ULI4
KIF26A-DTNR_158217.1 linkn.-118A>G upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF26AENST00000423312.7 linkc.25T>C p.Cys9Arg missense_variant Exon 1 of 15 5 NM_015656.2 ENSP00000388241.2 Q9ULI4
KIF26AENST00000697132.1 linkc.139-296T>C intron_variant Intron 1 of 14 ENSP00000513129.1 A0A8V8TM02

Frequencies

GnomAD3 genomes
AF:
0.000600
AC:
91
AN:
151584
Hom.:
1
Cov.:
33
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.:
1
Cov.:
31
AF XY:
0.000140
AC XY:
74
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:
91
AN:
151692
Hom.:
1
Cov.:
33
AF XY:
0.000566
AC XY:
42
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:
2
AN:
3462

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 09, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
19
DANN
Benign
0.94
Eigen
Benign
-0.99
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.40
T
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.81
L
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.084
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.14
T
Polyphen
0.099
B
Vest4
0.23
MutPred
0.39
Gain of MoRF binding (P = 7e-04);
MVP
0.39
MPC
4.9
ClinPred
0.33
T
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.

Other links and lift over

dbSNP: rs555804254; hg19: chr14-104605084; API