Variant 1-200977234-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_001252102.2(KIF21B):c.4303G>A(p.Val1435Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000822 in 1,460,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

KIF21B
NM_001252102.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84

Variant links:

Genes affected

KIF21B (HGNC:29442): (kinesin family member 21B) This gene encodes a member of the kinesin superfamily. Kinesins are ATP-dependent microtubule-based motor proteins that are involved in the intracellular transport of membranous organelles. Single nucleotide polymorphisms in this gene are associated with inflammatory bowel disease and multiple sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

KIF21B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, KIF21B

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF21B	NM_001252102.2 linkuse as main transcript	c.4303G>A	p.Val1435Ile	missense_variant	31/35	ENST00000461742.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF21B	ENST00000461742.7 linkuse as main transcript	c.4303G>A	p.Val1435Ile	missense_variant	31/35	1	NM_001252102.2	P3	O75037-4
KIF21B	ENST00000422435.2 linkuse as main transcript	c.4303G>A	p.Val1435Ile	missense_variant	31/35	1			O75037-1
KIF21B	ENST00000332129.6 linkuse as main transcript	c.4264G>A	p.Val1422Ile	missense_variant	30/34	1			O75037-2
KIF21B	ENST00000360529.9 linkuse as main transcript	c.4264G>A	p.Val1422Ile	missense_variant	30/34	1		A2	O75037-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250768

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1460726

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KIF21B-related Neurodevelopmental disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Apr 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.75

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.065

T;T;T;T

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.59

MutPred

0.35

.;Loss of MoRF binding (P = 0.1172);.;Loss of MoRF binding (P = 0.1172);

MVP

0.40

MPC

1.3

ClinPred

0.85

GERP RS

4.9

Varity_R

0.11

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over