16-29799998-C-T

Variant names:

• chr16-29799998-C-T
• rs235648
• NM_007317.3:c.1230C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007317.3(KIF22):​c.1230C>T​(p.Ile410Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 1,613,950 control chromosomes in the GnomAD database, including 783,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (65445 hom., cov: 32)
  • Exomes 𝑓: 0.99 (718142 hom.)
• Consequence: KIF22 NM_007317.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0740
• Publications: 17 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-29799998-C-T is Benign according to our data. Variant chr16-29799998-C-T is described in ClinVar as Benign. ClinVar VariationId is 1170585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.074 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007317.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF22	NM_007317.3	MANE Select	c.1230C>T	p.Ile410Ile	synonymous	Exon 8 of 14	NP_015556.1
	KIF22	NM_001256269.2		c.1026C>T	p.Ile342Ile	synonymous	Exon 9 of 15	NP_001243198.1
	KIF22	NM_001256270.1		c.1026C>T	p.Ile342Ile	synonymous	Exon 8 of 14	NP_001243199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF22	ENST00000160827.9	TSL:1 MANE Select	c.1230C>T	p.Ile410Ile	synonymous	Exon 8 of 14	ENSP00000160827.5
	KIF22	ENST00000569382.3	TSL:5	c.1230C>T	p.Ile410Ile	synonymous	Exon 8 of 14	ENSP00000456165.3
	KIF22	ENST00000689660.1		c.1182C>T	p.Ile394Ile	synonymous	Exon 8 of 14	ENSP00000509285.1

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139890 AN: 152138 Hom.: 65399 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.996

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.947

GnomAD2 exomes AF: 0.974 AC: 244585 AN: 251146 AF XY: 0.980

Gnomad AFR exome AF: 0.723

Gnomad AMR exome AF: 0.986

Gnomad ASJ exome AF: 0.988

Gnomad EAS exome AF: 0.934

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.986

GnomAD4 exome AF: 0.990 AC: 1447564 AN: 1461694 Hom.: 718142 Cov.: 55 AF XY: 0.992 AC XY: 721058 AN XY: 727168

African (AFR) AF: 0.725 AC: 24281 AN: 33468

American (AMR) AF: 0.985 AC: 44046 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 25822 AN: 26136

East Asian (EAS) AF: 0.953 AC: 37836 AN: 39700

South Asian (SAS) AF: 0.998 AC: 86082 AN: 86258

European-Finnish (FIN) AF: 1.00 AC: 53242 AN: 53242

Middle Eastern (MID) AF: 0.991 AC: 5713 AN: 5766

European-Non Finnish (NFE) AF: 0.999 AC: 1111445 AN: 1112006

Other (OTH) AF: 0.979 AC: 59097 AN: 60394

GnomAD4 genome AF: 0.919 AC: 139990 AN: 152256 Hom.: 65445 Cov.: 32 AF XY: 0.921 AC XY: 68561 AN XY: 74450

African (AFR) AF: 0.730 AC: 30284 AN: 41502

American (AMR) AF: 0.970 AC: 14837 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 3416 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4843 AN: 5176

South Asian (SAS) AF: 0.997 AC: 4817 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10624

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67965 AN: 68030

Other (OTH) AF: 0.947 AC: 2004 AN: 2116

Alfa AF: 0.970 Hom.: 41056

Bravo AF: 0.907

Asia WGS AF: 0.960 AC: 3339 AN: 3478

EpiCase AF: 0.998

EpiControl AF: 0.999

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Spondyloepimetaphyseal dysplasia with multiple dislocations (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.58
PhyloP100		-0.074
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=299/1	polymorphism (auto)

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: rs235648; hg19: chr16-29811319; COSMIC: COSV108033005; COSMIC: COSV108033005;