chr3-44774438-G-C

Variant names:

• chr3-44774438-G-C
• NM_020242.3:c.62+1G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020242.3(KIF15):​c.62+1G>C variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF15 NM_020242.3 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 0 publications found

Genes affected

KIF15 (HGNC:17273): (kinesin family member 15) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIF15 Gene-Disease associations (from GenCC):

• braddock-carey syndrome 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020242.3. 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
	KIF15	NM_020242.3	MANE Select	c.62+1G>C		splice_donor intron	N/A	NP_064627.1	Q9NS87-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF15	ENST00000326047.9	TSL:1 MANE Select	c.62+1G>C		splice_donor intron	N/A	ENSP00000324020.4	Q9NS87-1
	KIF15	ENST00000438321.5	TSL:1	n.20-816G>C		intron	N/A	ENSP00000406939.1	F8WC33
	KIF15	ENST00000917498.1		c.62+1G>C		splice_donor intron	N/A	ENSP00000587557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		4.3
Mutation Taster		=8/92	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.98		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.98		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-44815930;