20-32310525-G-C

Position:

• chr20-32310525-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2 PP2 PP3_Strong PP5

The NM_004798.4(KIF3B):​c.748G>C​(p.Glu250Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KIF3B NM_004798.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 10.0

Genes affected

KIF3B (HGNC:6320): (kinesin family member 3B) The protein encoded by this gene acts as a heterodimer with kinesin family member 3A to aid in chromosome movement during mitosis and meiosis. The encoded protein is a plus end-directed microtubule motor and can interact with the SMC3 subunit of the cohesin complex. In addition, the encoded protein may be involved in the intracellular movement of membranous organelles. This protein and kinesin family member 3A form the kinesin II subfamily of the kinesin superfamily. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KIF3B. . Gene score misZ 2.9986 (greater than the threshold 3.09). Trascript score misZ 3.7442 (greater than threshold 3.09). GenCC has associacion of gene with ciliopathy, retinitis pigmentosa 89.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.982
• PP5: Variant 20-32310525-G-C is Pathogenic according to our data. Variant chr20-32310525-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 973171.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr20-32310525-G-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF3B	NM_004798.4	c.748G>C	p.Glu250Gln	missense_variant	2/9	ENST00000375712.4	NP_004789.1
KIF3B	XM_047440589.1	c.748G>C	p.Glu250Gln	missense_variant	2/9		XP_047296545.1
KIF3B	XM_047440590.1	c.748G>C	p.Glu250Gln	missense_variant	2/9		XP_047296546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF3B	ENST00000375712.4	c.748G>C	p.Glu250Gln	missense_variant	2/9	1	NM_004798.4	ENSP00000364864.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 89 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.5	H
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.89		Gain of MoRF binding (P = 0.0365);
MVP		0.97
MPC		1.7
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.75
gMVP		0.94

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: rs2047794498; hg19: chr20-30898328;