Variant chr1-200974124-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000422435.2(KIF21B):c.4885A>G(p.Ile1629Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KIF21B
ENST00000422435.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33617115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2 linkuse as main transcript	c.4815-546A>G		intron_variant		ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000422435.2 linkuse as main transcript	c.4885A>G	p.Ile1629Val	missense_variant	35/35	1		ENSP00000411831		O75037-1
KIF21B	ENST00000332129.6 linkuse as main transcript	c.4846A>G	p.Ile1616Val	missense_variant	34/34	1		ENSP00000328494		O75037-2
KIF21B	ENST00000461742.7 linkuse as main transcript	c.4815-546A>G		intron_variant		1	NM_001252102.2	ENSP00000433808	P3	O75037-4
KIF21B	ENST00000360529.9 linkuse as main transcript	c.4776-546A>G		intron_variant		1		ENSP00000353724	A2	O75037-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453222

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722746

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.4846A>G (p.I1616V) alteration is located in exon 34 (coding exon 34) of the KIF21B gene. This alteration results from a A to G substitution at nucleotide position 4846, causing the isoleucine (I) at amino acid position 1616 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.030

.;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

0.69

.;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.22

Sift

Benign

0.080

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.88

P;P

Vest4

0.44

MutPred

0.28

.;Gain of methylation at K1630 (P = 0.0735);

MVP

0.46

MPC

0.78

ClinPred

0.94

GERP RS

4.5

Varity_R

0.11

gMVP

0.30

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over