Variant 1-200979689-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001252102.2(KIF21B):c.4006G>A(p.Val1336Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,394,454 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: 0.0000014 ( 0 hom. )

Consequence

KIF21B
NM_001252102.2 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=0.31007636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF21B	NM_001252102.2 linkuse as main transcript	c.4006G>A	p.Val1336Ile	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.4006G>A	p.Val1336Ile	missense_variant	30/35	1	NM_001252102.2	ENSP00000433808	P3	O75037-4
KIF21B	ENST00000422435.2 linkuse as main transcript	c.4006G>A	p.Val1336Ile	missense_variant	30/35	1		ENSP00000411831		O75037-1
KIF21B	ENST00000332129.6 linkuse as main transcript	c.3967G>A	p.Val1323Ile	missense_variant	29/34	1		ENSP00000328494		O75037-2
KIF21B	ENST00000360529.9 linkuse as main transcript	c.3967G>A	p.Val1323Ile	missense_variant	29/34	1		ENSP00000353724	A2	O75037-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1394454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000567

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 16, 2023

Not observed at significant frequency in large population cohorts (gnomAD); 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

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

.;.;.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;L;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.66

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.049

D;T;D;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

1.0

D;.;.;D

Vest4

0.39

MutPred

0.30

.;Gain of ubiquitination at K1331 (P = 0.1832);.;Gain of ubiquitination at K1331 (P = 0.1832);

MVP

0.30

MPC

1.3

ClinPred

0.93

GERP RS

5.0

Varity_R

0.15

gMVP

0.16

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