14-104138747-T-G

Variant names:

• chr14-104138747-T-G
• rs555804254
• NM_015656.2:c.25T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015656.2(KIF26A):​c.25T>G​(p.Cys9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000792 in 1,263,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. C9R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: KIF26A NM_015656.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0220
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20993686).

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>G	p.Cys9Gly	missense	Exon 1 of 15	NP_056471.1	Q9ULI4
	KIF26A-DT	NR_158217.1		n.-118A>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF26A	ENST00000423312.7	TSL:5 MANE Select	c.25T>G	p.Cys9Gly	missense	Exon 1 of 15	ENSP00000388241.2	Q9ULI4
	KIF26A	ENST00000926957.1		c.25T>G	p.Cys9Gly	missense	Exon 1 of 15	ENSP00000597016.1
	KIF26A	ENST00000697132.1		c.139-296T>G		intron	N/A	ENSP00000513129.1	A0A8V8TM02

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151584 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000720 AC: 8 AN: 1111688 Hom.: 0 Cov.: 31 AF XY: 0.00000943 AC XY: 5 AN XY: 530152

African (AFR) AF: 0.00 AC: 0 AN: 22782

American (AMR) AF: 0.00 AC: 0 AN: 8502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14698

East Asian (EAS) AF: 0.00 AC: 0 AN: 26276

South Asian (SAS) AF: 0.00 AC: 0 AN: 29082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3012

European-Non Finnish (NFE) AF: 0.00000852 AC: 8 AN: 939062

Other (OTH) AF: 0.00 AC: 0 AN: 44748

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151584 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74042

African (AFR) AF: 0.00 AC: 0 AN: 41304

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67866

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.77
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.39	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.022
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.31	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.37		Gain of MoRF binding (P = 0.0559)
MVP		0.39
MPC		2.6
ClinPred		0.11	T
GERP RS		-1.1
PromoterAI		0.072	Neutral
Varity_R		0.50
gMVP		0.29
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs555804254; hg19: chr14-104605084;