chr1-245688693-G-C

Position:

• chr1-245688693-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_018012.4(KIF26B):​c.5710G>C​(p.Asp1904His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,606,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1904N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: KIF26B NM_018012.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.79

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]

LOC105373265 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831
• BS2: High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF26B	NM_018012.4	c.5710G>C	p.Asp1904His	missense_variant	12/15	ENST00000407071.7	NP_060482.2
LOC105373265	XR_007066988.1	n.657-4242C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF26B	ENST00000407071.7	c.5710G>C	p.Asp1904His	missense_variant	12/15	1	NM_018012.4	ENSP00000385545.2
KIF26B	ENST00000366518.4	c.4567G>C	p.Asp1523His	missense_variant	9/12	5		ENSP00000355475.4

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000162 AC: 36 AN: 222636 Hom.: 0 AF XY: 0.000146 AC XY: 18 AN XY: 123444

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.000214

Gnomad EAS exome AF: 0.000412

Gnomad SAS exome AF: 0.000173

Gnomad FIN exome AF: 0.000202

Gnomad NFE exome AF: 0.0000931

Gnomad OTH exome AF: 0.000362

GnomAD4 exome AF: 0.000102 AC: 148 AN: 1454376 Hom.: 0 Cov.: 34 AF XY: 0.0000899 AC XY: 65 AN XY: 723024

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.0000904

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.000304

Gnomad4 SAS exome AF: 0.000129

Gnomad4 FIN exome AF: 0.000216

Gnomad4 NFE exome AF: 0.0000874

Gnomad4 OTH exome AF: 0.0000666

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74502

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.000144 AC: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.77	D;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.5	D;D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.90
MVP		0.88
MPC		0.36
ClinPred		0.24	T
GERP RS		5.3
Varity_R		0.76
gMVP		0.73

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

Other links and lift over

dbSNP: rs749953234; hg19: chr1-245851995;