dbSNP rs758134092: KIF1B:p.Lys7Arg (chr1-10232348-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365951.3(KIF1B):c.20A>G(p.Lys7Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. K7M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KIF1B
NM_001365951.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.65

Variant links:

Genes affected

KIF1B (HGNC:16636): (kinesin family member 1B) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in chemical synaptic transmission; dense core granule cytoskeletal transport; and vesicle-mediated transport. Predicted to act upstream of or within mitochondrion transport along microtubule. Predicted to be located in cytoplasmic vesicle membrane and neuron projection. Predicted to be part of kinesin complex. Predicted to be active in several cellular components, including axon; dendrite; and microtubule. Implicated in Charcot-Marie-Tooth disease type 2A1; carcinoma (multiple); multiple sclerosis; neuroblastoma; and pheochromocytoma. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

KIF1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3 link	c.20A>G	p.Lys7Arg	missense_variant	Exon 2 of 49	ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1 link	c.20A>G	p.Lys7Arg	missense_variant	Exon 2 of 49		NM_001365951.3	ENSP00000502065.1		O60333-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726986

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

.;.;D;.;.;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

.;D;D;D;D;D;D

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.71

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.36

MutationAssessor

Benign

0.29

N;N;N;N;N;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.9

D;D;D;D;D;.;.

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0060

D;D;D;D;D;.;.

Sift4G

Uncertain

0.0060

D;D;D;D;D;D;D

Polyphen

0.63

P;D;B;P;.;P;.

Vest4

0.87

MutPred

0.42

Loss of ubiquitination at K7 (P = 0.0233);Loss of ubiquitination at K7 (P = 0.0233);Loss of ubiquitination at K7 (P = 0.0233);Loss of ubiquitination at K7 (P = 0.0233);Loss of ubiquitination at K7 (P = 0.0233);Loss of ubiquitination at K7 (P = 0.0233);Loss of ubiquitination at K7 (P = 0.0233);

MVP

0.96

MPC

1.7

ClinPred

0.93

GERP RS

5.4

Varity_R

0.76

gMVP

0.91

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over