chr1-245156640-G-A

Position:

• chr1-245156640-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_018012.4(KIF26B):​c.422G>A​(p.Arg141Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000153 in 1,369,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: KIF26B NM_018012.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

Genes affected

KIF26B (HGNC:25484): (kinesin family member 26B) The protein encoded by this gene is an intracellular motor protein thought to transport organelles along microtubules. The encoded protein is required for kidney development. Elevated levels of this protein have been found in some breast and colorectal cancers. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28871292).
• BS2: High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF26B	NM_018012.4	c.422G>A	p.Arg141Lys	missense_variant	2/15	ENST00000407071.7	NP_060482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF26B	ENST00000407071.7	c.422G>A	p.Arg141Lys	missense_variant	2/15	1	NM_018012.4	ENSP00000385545.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000153 AC: 21 AN: 1369816 Hom.: 0 Cov.: 32 AF XY: 0.0000133 AC XY: 9 AN XY: 675990

Gnomad4 AFR exome AF: 0.00

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: 0.0000196

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

The c.422G>A (p.R141K) alteration is located in exon 2 (coding exon 2) of the KIF26B gene. This alteration results from a G to A substitution at nucleotide position 422, causing the arginine (R) at amino acid position 141 to be replaced by a lysine (K). 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	0.26
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.027	D
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.43
Sift	Benign	0.12	T
Sift4G	Benign	0.45	T
Polyphen		0.61	P
Vest4		0.15
MutPred		0.54		Loss of MoRF binding (P = 0.0958);
MVP		0.50
MPC		0.31
ClinPred		0.62	D
GERP RS		4.2
Varity_R		0.27
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-245319942; COSMIC: COSV105343614;