16-29802912-T-G

Variant names:

• chr16-29802912-T-G
• rs1555499767
• NM_007317.3:c.1424T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007317.3(KIF22):​c.1424T>G​(p.Val475Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V475V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: KIF22 NM_007317.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia with multiple dislocations

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23768923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF22	NM_007317.3	c.1424T>G	p.Val475Gly	missense_variant	Exon 9 of 14	ENST00000160827.9	NP_015556.1
KIF22	NM_001256269.2	c.1220T>G	p.Val407Gly	missense_variant	Exon 10 of 15		NP_001243198.1
KIF22	NM_001256270.1	c.1220T>G	p.Val407Gly	missense_variant	Exon 9 of 14		NP_001243199.1
KIF22	XM_047434094.1	c.1424T>G	p.Val475Gly	missense_variant	Exon 9 of 11		XP_047290050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF22	ENST00000160827.9	c.1424T>G	p.Val475Gly	missense_variant	Exon 9 of 14	1	NM_007317.3	ENSP00000160827.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spondyloepimetaphyseal dysplasia with multiple dislocations Uncertain:1

Nov 08, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.61	.;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	.;M;.;.
PhyloP100		2.7
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Uncertain	0.028	D;D;D;D
Polyphen		0.44	.;B;.;.
Vest4		0.39
MutPred		0.39		.;Loss of stability (P = 0.0605);.;.;
MVP		0.84
MPC		0.54
ClinPred		0.57	D
GERP RS		5.6
Varity_R		0.21
gMVP		0.57

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

Other links and lift over

dbSNP: rs1555499767; hg19: chr16-29814233;