Variant chr1-200979701-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000461742.7(KIF21B):c.3994A>T(p.Met1332Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,378,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

KIF21B
ENST00000461742.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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=0.2675565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2 linkuse as main transcript	c.3994A>T	p.Met1332Leu	missense_variant	30/35	ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7 linkuse as main transcript	c.3994A>T	p.Met1332Leu	missense_variant	30/35	1	NM_001252102.2	ENSP00000433808	P3	O75037-4
KIF21B	ENST00000422435.2 linkuse as main transcript	c.3994A>T	p.Met1332Leu	missense_variant	30/35	1		ENSP00000411831		O75037-1
KIF21B	ENST00000332129.6 linkuse as main transcript	c.3955A>T	p.Met1319Leu	missense_variant	29/34	1		ENSP00000328494		O75037-2
KIF21B	ENST00000360529.9 linkuse as main transcript	c.3955A>T	p.Met1319Leu	missense_variant	29/34	1		ENSP00000353724	A2	O75037-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000533

AC:

AN:

187726

Hom.:

AF XY:

0.00000988

AC XY:

AN XY:

101202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000426

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.25e-7

AC:

AN:

1378744

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

679896

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000291

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:

0.00

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 provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 11, 2023

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.027

.;.;.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.012

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.84

T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-1.0

.;N;.;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.95

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.16

T;T;T;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.83

P;.;.;B

Vest4

0.47

MutPred

0.53

.;Loss of catalytic residue at M1332 (P = 0.0057);.;Loss of catalytic residue at M1332 (P = 0.0057);

MVP

0.37

MPC

1.3

ClinPred

0.68

GERP RS

5.0

Varity_R

0.26

gMVP

0.37

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