15-69417409-C-A

Variant names:

• chr15-69417409-C-A
• rs3759826
• NM_001367805.3:c.108C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001367805.3(KIF23):​c.108C>A​(p.Gly36Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 1,612,196 control chromosomes in the GnomAD database, including 3,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (989 hom., cov: 32)
  • Exomes 𝑓: 0.032 (2297 hom.)
• Consequence: KIF23 NM_001367805.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.629
• Publications: 11 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 15-69417409-C-A is Benign according to our data. Variant chr15-69417409-C-A is described in ClinVar as Benign. ClinVar VariationId is 1182474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.629 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

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.108C>A	p.Gly36Gly	synonymous	Exon 3 of 24	NP_001354734.1	A0A7I2V5Y5
	KIF23	NM_138555.4		c.108C>A	p.Gly36Gly	synonymous	Exon 3 of 23	NP_612565.1	Q02241-1
	KIF23	NM_001367804.2		c.108C>A	p.Gly36Gly	synonymous	Exon 3 of 22	NP_001354733.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF23	ENST00000679126.1	MANE Select	c.108C>A	p.Gly36Gly	synonymous	Exon 3 of 24	ENSP00000504770.1	A0A7I2V5Y5
	KIF23	ENST00000260363.9	TSL:1	c.108C>A	p.Gly36Gly	synonymous	Exon 3 of 23	ENSP00000260363.4	Q02241-1
	KIF23	ENST00000352331.8	TSL:1	c.108C>A	p.Gly36Gly	synonymous	Exon 3 of 22	ENSP00000304978.6	Q02241-2

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12730 AN: 152084 Hom.: 985 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0698

GnomAD2 exomes AF: 0.0633 AC: 15797 AN: 249670 AF XY: 0.0541

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.00657

Gnomad EAS exome AF: 0.186

Gnomad FIN exome AF: 0.0407

Gnomad NFE exome AF: 0.0181

Gnomad OTH exome AF: 0.0410

GnomAD4 exome AF: 0.0323 AC: 47217 AN: 1459994 Hom.: 2297 Cov.: 32 AF XY: 0.0309 AC XY: 22409 AN XY: 726302

African (AFR) AF: 0.192 AC: 6407 AN: 33410

American (AMR) AF: 0.147 AC: 6528 AN: 44334

Ashkenazi Jewish (ASJ) AF: 0.00617 AC: 161 AN: 26090

East Asian (EAS) AF: 0.191 AC: 7546 AN: 39566

South Asian (SAS) AF: 0.0208 AC: 1788 AN: 85854

European-Finnish (FIN) AF: 0.0401 AC: 2143 AN: 53378

Middle Eastern (MID) AF: 0.0271 AC: 156 AN: 5760

European-Non Finnish (NFE) AF: 0.0181 AC: 20087 AN: 1111290

Other (OTH) AF: 0.0398 AC: 2401 AN: 60312

GnomAD4 genome AF: 0.0838 AC: 12756 AN: 152202 Hom.: 989 Cov.: 32 AF XY: 0.0853 AC XY: 6347 AN XY: 74410

African (AFR) AF: 0.195 AC: 8096 AN: 41492

American (AMR) AF: 0.109 AC: 1670 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.178 AC: 922 AN: 5178

South Asian (SAS) AF: 0.0243 AC: 117 AN: 4824

European-Finnish (FIN) AF: 0.0433 AC: 459 AN: 10610

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0189 AC: 1287 AN: 68024

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0379 Hom.: 487

Bravo AF: 0.0946

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	9.0
DANN	Benign	0.73
PhyloP100		0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs3759826; hg19: chr15-69709748; COSMIC: COSV52980052; COSMIC: COSV52980052;