chr3-44786530-G-A

Variant names:

• chr3-44786530-G-A
• NM_020242.3:c.595G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020242.3(KIF15):​c.595G>A​(p.Gly199Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF15 NM_020242.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

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.595G>A	p.Gly199Ser	missense	Exon 7 of 35	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.595G>A	p.Gly199Ser	missense	Exon 7 of 35	ENSP00000324020.4	Q9NS87-1
	KIF15	ENST00000438321.5	TSL:1	n.*300G>A		non_coding_transcript_exon	Exon 6 of 34	ENSP00000406939.1	F8WC33
	KIF15	ENST00000438321.5	TSL:1	n.*300G>A		3_prime_UTR	Exon 6 of 34	ENSP00000406939.1	F8WC33

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		10
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.037	D
Polyphen		0.99	D
Vest4		0.87
MutPred		0.61		Gain of helix (P = 0.0034)
MVP		0.70
MPC		0.79
ClinPred		0.94	D
GERP RS		5.8
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.31
gMVP		0.61
Mutation Taster		=48/52	disease causing

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

Other links and lift over

hg19: chr3-44828022;