16-29790787-A-T

Position:

• chr16-29790787-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007317.3(KIF22):​c.28A>T​(p.Arg10Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF22 NM_007317.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.784

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF22	NM_007317.3	c.28A>T	p.Arg10Trp	missense_variant	1/14	ENST00000160827.9	NP_015556.1
KIF22	XM_047434094.1	c.28A>T	p.Arg10Trp	missense_variant	1/11		XP_047290050.1
KIF22	XM_047434095.1	c.28A>T	p.Arg10Trp	missense_variant	1/9		XP_047290051.1
KIF22	NM_001256269.2	c.-226A>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	c.28A>T	p.Arg10Trp	missense_variant	1/14	1	NM_007317.3	ENSP00000160827	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450642 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720500

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 09, 2022

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 10 of the KIF22 protein (p.Arg10Trp). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with KIF22-related conditions. This variant is not present in population databases (gnomAD no frequency). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.0038	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.89	D;D;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.011	D
Polyphen		0.93	P
Vest4		0.48
MutPred		0.27		Loss of phosphorylation at T7 (P = 0.0447);
MVP		0.82
MPC		0.39
ClinPred		0.64	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29802108;