Genetic Variant KIF23:c.-29C>T (chr15-69414437-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001367805.3(KIF23):c.-29C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,581,124 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 16 hom. )

Consequence

KIF23
NM_001367805.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0700

Variant links:

Genes affected

KIF23 (HGNC:6392): (kinesin family member 23) The protein encoded by this gene is a member of kinesin-like protein family. This family includes microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. This protein has been shown to cross-bridge antiparallel microtubules and drive microtubule movement in vitro. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2013]

KIF23 links:

KIF23-AS1 (HGNC:27075): (KIF23 and PAQR5 antisense RNA 1)

KIF23-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BS2

High AC in GnomAd4 at 414 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF23	NM_001367805.3 link	c.-29C>T		5_prime_UTR_variant	Exon 1 of 24	ENST00000679126.1	NP_001354734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF23	ENST00000679126 link	c.-29C>T		5_prime_UTR_variant	Exon 1 of 24		NM_001367805.3	ENSP00000504770.1		A0A7I2V5Y5

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

414

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00479

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00219

AC:

421

AN:

192398

AF XY:

0.00219

show subpopulations

Gnomad AFR exome

AF:

0.000920

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000465

Gnomad NFE exome

AF:

0.00411

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00413

AC:

5894

AN:

1428756

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

2828

AN XY:

707698

show subpopulations

Gnomad4 AFR exome

AF:

0.000457

AC:

AN:

32854

Gnomad4 AMR exome

AF:

0.00132

AC:

AN:

40188

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25490

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

38072

Gnomad4 SAS exome

AF:

0.000898

AC:

AN:

81298

Gnomad4 FIN exome

AF:

0.000417

AC:

AN:

50414

Gnomad4 NFE exome

AF:

0.00503

AC:

5508

AN:

1095766

Gnomad4 Remaining exome

AF:

0.00373

AC:

220

AN:

59020

Heterozygous variant carriers

291

582

874

1165

1456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00272

AC:

414

AN:

152368

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000938

AC:

0.000937861

AN:

0.000937861

Gnomad4 AMR

AF:

0.00222

AC:

0.00222019

AN:

0.00222019

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000828

AC:

0.000827815

AN:

0.000827815

Gnomad4 FIN

AF:

0.000471

AC:

0.000470544

AN:

0.000470544

Gnomad4 NFE

AF:

0.00479

AC:

0.00479172

AN:

0.00479172

Gnomad4 OTH

AF:

0.00284

AC:

0.00283554

AN:

0.00283554

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00276

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Nov 10, 2021

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.6

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=296/4

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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