Genetic Variant KIF26A:p.Ser31Tyr (chr14-104139092-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_015656.2(KIF26A):c.92C>A(p.Ser31Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000461 in 1,302,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000046 ( 0 hom. )

Consequence

KIF26A
NM_015656.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.760

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 Gene-Disease associations (from GenCC):

complex cortical dysplasia with other brain malformations
Inheritance: AR Classification: STRONG Submitted by: ClinGen
cortical dysplasia, complex, with other brain malformations 11
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Baylor College of Medicine Research Center, Labcorp Genetics (formerly Invitae)

KIF26A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity KI26A_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3000736).

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.92C>A	p.Ser31Tyr	missense	Exon 2 of 15	NP_056471.1	Q9ULI4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF26A	ENST00000423312.7	TSL:5 MANE Select	c.92C>A	p.Ser31Tyr	missense	Exon 2 of 15	ENSP00000388241.2	Q9ULI4
KIF26A	ENST00000315264.7	TSL:1	c.-326C>A		5_prime_UTR	Exon 1 of 14	ENSP00000325452.7	C9JFF0
KIF26A	ENST00000697132.1		c.188C>A	p.Ser63Tyr	missense	Exon 2 of 15	ENSP00000513129.1	A0A8V8TM02

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000461

AC:

AN:

1302820

Hom.:

Cov.:

AF XY:

0.00000313

AC XY:

AN XY:

639956

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25554

American (AMR)

AF:

0.00

AC:

AN:

20058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22176

East Asian (EAS)

AF:

0.00

AC:

AN:

28338

South Asian (SAS)

AF:

0.00

AC:

AN:

66414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3884

European-Non Finnish (NFE)

AF:

0.00000578

AC:

AN:

1038806

Other (OTH)

AF:

0.00

AC:

AN:

53634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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

Cov.:

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

0.20

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.55

PhyloP100

0.76

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.19

Sift

Uncertain

0.010

Sift4G

Uncertain

0.016

Polyphen

0.46

Vest4

0.13

MutPred

0.28

Loss of glycosylation at S31 (P = 0.0302)

MVP

0.71

MPC

3.1

ClinPred

0.45

GERP RS

2.0

PromoterAI

-0.057

Neutral

(source)

Varity_R

0.14

gMVP

0.27

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over