10-32022139-C-AA

Variant names:

• chr10-32022139-C-AA
• NM_004521.3:c.2032+1delGinsTT

Variant summary

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

The NM_004521.3(KIF5B):​c.2032+1delGinsTT variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF5B NM_004521.3 splice_donor, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

KIF5B (HGNC:6324): (kinesin family member 5B) Enables identical protein binding activity; microtubule binding activity; and microtubule motor activity. Involved in several processes, including lysosome localization; natural killer cell mediated cytotoxicity; and positive regulation of protein localization to plasma membrane. Located in centriolar satellite; cytosol; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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
KIF5B	NM_004521.3	c.2032+1delGinsTT		splice_donor_variant, intron_variant	Intron 17 of 25	ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1	c.2032+1delGinsTT		splice_donor_variant, intron_variant	Intron 17 of 24		XP_047281158.1
KIF5B	XM_047425203.1	c.1750+1delGinsTT		splice_donor_variant, intron_variant	Intron 18 of 26		XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.2032+1delGinsTT		splice_donor_variant, intron_variant	Intron 17 of 25	1	NM_004521.3	ENSP00000307078.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Apr 28, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015) -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr10-32311067;