14-104152039-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting

The NM_015656.2(KIF26A):​c.313C>T​(p.Leu105Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,612,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

KIF26A
NM_015656.2 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10468072).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000092 (14/152130) while in subpopulation AFR AF= 0.00029 (12/41398). AF 95% confidence interval is 0.000167. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 32. 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.313C>T p.Leu105Phe missense_variant Exon 3 of 15 ENST00000423312.7 NP_056471.1 Q9ULI4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF26AENST00000423312.7 linkc.313C>T p.Leu105Phe missense_variant Exon 3 of 15 5 NM_015656.2 ENSP00000388241.2 Q9ULI4
KIF26AENST00000315264 linkc.-105C>T 5_prime_UTR_variant Exon 2 of 14 1 ENSP00000325452.7 C9JFF0
KIF26AENST00000697132.1 linkc.409C>T p.Leu137Phe missense_variant Exon 3 of 15 ENSP00000513129.1 A0A8V8TM02

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000290
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD3 exomes
AF:
0.0000207
AC:
5
AN:
242102
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
132994
show subpopulations
Gnomad AFR exome
AF:
0.000348
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000753
AC:
11
AN:
1460400
Hom.:
0
Cov.:
32
AF XY:
0.00000826
AC XY:
6
AN XY:
726510
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.000290
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000762
Hom.:
0
Bravo
AF:
0.000147
ExAC
AF:
0.0000166
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 07, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.313C>T (p.L105F) alteration is located in exon 3 (coding exon 3) of the KIF26A gene. This alteration results from a C to T substitution at nucleotide position 313, causing the leucine (L) at amino acid position 105 to be replaced by a phenylalanine (F). 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
Benign
0.22
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
17
DANN
Uncertain
0.99
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.66
T
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
0.15
N
REVEL
Benign
0.095
Sift
Benign
0.21
T
Sift4G
Benign
0.19
T
Polyphen
0.0020
B
Vest4
0.30
MVP
0.94
MPC
0.33
ClinPred
0.057
T
GERP RS
3.3
Varity_R
0.097
gMVP
0.11

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: rs756957352; hg19: chr14-104618376; API