Variant 16-29790794-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_007317.3(KIF22):c.35G>T(p.Arg12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,451,830 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: 0.000017 ( 0 hom. )

Consequence

KIF22
NM_007317.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

Variant links:

Genes affected

KIF22 (HGNC:6391): (kinesin family member 22) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. The C-terminal half of this protein has been shown to bind DNA. Studies with the Xenopus homolog suggests its essential role in metaphase chromosome alignment and maintenance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

KIF22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KIF22	NM_007317.3 linkuse as main transcript	c.35G>T	p.Arg12Leu	missense_variant	1/14	ENST00000160827.9	NP_015556.1
KIF22	XM_047434094.1 linkuse as main transcript	c.35G>T	p.Arg12Leu	missense_variant	1/11		XP_047290050.1
KIF22	XM_047434095.1 linkuse as main transcript	c.35G>T	p.Arg12Leu	missense_variant	1/9		XP_047290051.1
KIF22	NM_001256269.2 linkuse as main transcript	c.-219G>T		5_prime_UTR_variant	1/15		NP_001243198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF22	ENST00000160827.9 linkuse as main transcript	c.35G>T	p.Arg12Leu	missense_variant	1/14	1	NM_007317.3	ENSP00000160827	P2	Q14807-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000446

AC:

AN:

224174

Hom.:

AF XY:

0.0000328

AC XY:

AN XY:

122032

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1451830

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

721172

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:

0.0000217

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000830

AC:

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

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 2023

This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 12 of the KIF22 protein (p.Arg12Leu). This variant is present in population databases (rs753183645, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with KIF22-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.16

REVEL

Benign

0.27

Sift

Benign

0.080

Sift4G

Uncertain

0.023

Polyphen

0.99

Vest4

0.55

MutPred

0.31

Loss of MoRF binding (P = 0.1264);

MVP

0.82

MPC

0.94

ClinPred

0.75

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.36

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