dbSNP rs146916477: KIF21B:p.Thr1464Met (chr1-200976828-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001252102.2(KIF21B):c.4391C>T(p.Thr1464Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000706 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

KIF21B
NM_001252102.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27563608).

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF21B	NM_001252102.2 link	c.4391C>T	p.Thr1464Met	missense_variant	Exon 32 of 35	ENST00000461742.7	NP_001239031.1	O75037-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF21B	ENST00000461742.7 link	c.4391C>T	p.Thr1464Met	missense_variant	Exon 32 of 35	1	NM_001252102.2	ENSP00000433808.1	O75037-4
KIF21B	ENST00000422435.2 link	c.4391C>T	p.Thr1464Met	missense_variant	Exon 32 of 35	1		ENSP00000411831.2	O75037-1
KIF21B	ENST00000332129.6 link	c.4352C>T	p.Thr1451Met	missense_variant	Exon 31 of 34	1		ENSP00000328494.2	O75037-2
KIF21B	ENST00000360529.9 link	c.4352C>T	p.Thr1451Met	missense_variant	Exon 31 of 34	1		ENSP00000353724.5	O75037-3

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

250706

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1461398

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000223

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000700

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000751

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4352C>T (p.T1451M) alteration is located in exon 31 (coding exon 31) of the KIF21B gene. This alteration results from a C to T substitution at nucleotide position 4352, causing the threonine (T) at amino acid position 1451 to be replaced by a methionine (M). 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

Benign

0.088

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;.;.;T

Eigen

Benign

0.016

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

.;L;.;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.68

P;.;.;P

Vest4

0.59

MVP

0.41

MPC

1.4

ClinPred

0.093

GERP RS

4.0

Varity_R

0.033

gMVP

0.22

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