16-29790757-G-A

Variant names:

• chr16-29790757-G-A
• rs144408025
• NM_007317.3:c.-3G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007317.3(KIF22):​c.-3G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 1,592,204 control chromosomes in the GnomAD database, including 504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (269 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (235 hom.)
• Consequence: KIF22 NM_007317.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00
• 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 16-29790757-G-A is Benign according to our data. Variant chr16-29790757-G-A is described in ClinVar as Benign. ClinVar VariationId is 193354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF22	NM_007317.3	MANE Select	c.-3G>A		5_prime_UTR	Exon 1 of 14	NP_015556.1	Q14807-1
	KIF22	NM_001256269.2		c.-256G>A		5_prime_UTR	Exon 1 of 15	NP_001243198.1	Q14807-2
	KIF22	NM_001256270.1		c.-599G>A		upstream_gene	N/A	NP_001243199.1	Q14807-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF22	ENST00000160827.9	TSL:1 MANE Select	c.-3G>A		5_prime_UTR	Exon 1 of 14	ENSP00000160827.5	Q14807-1
	KIF22	ENST00000569382.3	TSL:5	c.-3G>A		5_prime_UTR	Exon 1 of 14	ENSP00000456165.3	H3BRB3
	KIF22	ENST00000936369.1		c.-3G>A		5_prime_UTR	Exon 1 of 15	ENSP00000606428.1

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4912 AN: 152148 Hom.: 268 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00792 AC: 1623 AN: 204848 AF XY: 0.00595

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00572

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000479

Gnomad OTH exome AF: 0.00503

GnomAD4 exome AF: 0.00351 AC: 5056 AN: 1439938 Hom.: 235 Cov.: 32 AF XY: 0.00300 AC XY: 2144 AN XY: 714010

African (AFR) AF: 0.110 AC: 3655 AN: 33162

American (AMR) AF: 0.00621 AC: 258 AN: 41570

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 305 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 38786

South Asian (SAS) AF: 0.000312 AC: 26 AN: 83276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51138

Middle Eastern (MID) AF: 0.00456 AC: 26 AN: 5700

European-Non Finnish (NFE) AF: 0.000269 AC: 296 AN: 1101174

Other (OTH) AF: 0.00824 AC: 490 AN: 59466

GnomAD4 genome AF: 0.0323 AC: 4920 AN: 152266 Hom.: 269 Cov.: 33 AF XY: 0.0308 AC XY: 2293 AN XY: 74468

African (AFR) AF: 0.111 AC: 4605 AN: 41558

American (AMR) AF: 0.0121 AC: 185 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68000

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0104 Hom.: 17

Bravo AF: 0.0364

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.0
PromoterAI		0.19	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs144408025; hg19: chr16-29802078;