15-69414464-C-T

Variant names:

• chr15-69414464-C-T
• rs142968400
• NM_001367805.3:c.-2C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001367805.3(KIF23):​c.-2C>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 0.000707 in 1,589,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00073 (0 hom.)
• Consequence: KIF23 NM_001367805.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.180
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 15-69414464-C-T is Benign according to our data. Variant chr15-69414464-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3388365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 73 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367805.3. 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
	KIF23	NM_001367805.3	MANE Select	c.-2C>T		5_prime_UTR	Exon 1 of 24	NP_001354734.1	A0A7I2V5Y5
	KIF23	NM_138555.4		c.-2C>T		5_prime_UTR	Exon 1 of 23	NP_612565.1	Q02241-1
	KIF23	NM_001367804.2		c.-2C>T		5_prime_UTR	Exon 1 of 22	NP_001354733.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF23	ENST00000679126.1	MANE Select	c.-2C>T		5_prime_UTR	Exon 1 of 24	ENSP00000504770.1	A0A7I2V5Y5
	KIF23	ENST00000260363.9	TSL:1	c.-2C>T		5_prime_UTR	Exon 1 of 23	ENSP00000260363.4	Q02241-1
	KIF23	ENST00000352331.8	TSL:1	c.-2C>T		5_prime_UTR	Exon 1 of 22	ENSP00000304978.6	Q02241-2

Frequencies

GnomAD3 genomes AF: 0.000479 AC: 73 AN: 152264 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000379 AC: 78 AN: 205918 AF XY: 0.000403

Gnomad AFR exome AF: 0.000252

Gnomad AMR exome AF: 0.000266

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000168

Gnomad NFE exome AF: 0.000690

Gnomad OTH exome AF: 0.000390

GnomAD4 exome AF: 0.000731 AC: 1050 AN: 1436970 Hom.: 0 Cov.: 30 AF XY: 0.000679 AC XY: 484 AN XY: 712530

African (AFR) AF: 0.000304 AC: 10 AN: 32860

American (AMR) AF: 0.000384 AC: 16 AN: 41614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25628

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38478

South Asian (SAS) AF: 0.00 AC: 0 AN: 82150

European-Finnish (FIN) AF: 0.000293 AC: 15 AN: 51212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 0.000893 AC: 983 AN: 1100178

Other (OTH) AF: 0.000421 AC: 25 AN: 59332

GnomAD4 genome AF: 0.000479 AC: 73 AN: 152264 Hom.: 0 Cov.: 33 AF XY: 0.000323 AC XY: 24 AN XY: 74390

African (AFR) AF: 0.000145 AC: 6 AN: 41472

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68048

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.000459 Hom.: 0

Bravo AF: 0.000468

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		-0.18
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism

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: rs142968400; hg19: chr15-69706803;