3-44775355-C-T

Variant names:

• chr3-44775355-C-T
• NM_020242.3:c.164C>T

Variant summary

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

The NM_020242.3(KIF15):​c.164C>T​(p.Ser55Phe) 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 Likely risk allele (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KIF15 NM_020242.3 missense
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: 7.70
• 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, 0.812

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.164C>T	p.Ser55Phe	missense	Exon 3 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.164C>T	p.Ser55Phe	missense	Exon 3 of 35	ENSP00000324020.4	Q9NS87-1
	KIF15	ENST00000438321.5	TSL:1	n.121C>T		non_coding_transcript_exon	Exon 2 of 34	ENSP00000406939.1	F8WC33
	KIF15	ENST00000917498.1		c.164C>T	p.Ser55Phe	missense	Exon 3 of 36	ENSP00000587557.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely risk allele

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary fibrosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.030	D
Polyphen		0.92	P
Vest4		0.77
MutPred		0.39		Loss of disorder (P = 0.0031)
MVP		0.85
MPC		0.84
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.48
gMVP		0.56
Mutation Taster		=38/62	disease causing

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

hg19: chr3-44816847;