3-44775355-C-T

Position:

• chr3-44775355-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The ENST00000326047.9(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 ENST00000326047.9 missense
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: 7.70

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812
• PP5: Variant 3-44775355-C-T is Pathogenic according to our data. Variant chr3-44775355-C-T is described in ClinVar as [Likely_risk_allele]. Clinvar id is 1695968.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF15	NM_020242.3	c.164C>T	p.Ser55Phe	missense_variant	3/35	ENST00000326047.9	NP_064627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF15	ENST00000326047.9	c.164C>T	p.Ser55Phe	missense_variant	3/35	1	NM_020242.3	ENSP00000324020	P1
KIF15	ENST00000438321.5	c.121C>T	p.Pro41Ser	missense_variant, NMD_transcript_variant	2/34	1		ENSP00000406939
KIF15	ENST00000481166.6	c.-83-5530C>T		intron_variant		5		ENSP00000425499

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary fibrosis Pathogenic:1

Likely risk allele, no assertion criteria provided

research

Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center

Jun 09, 2022

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Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	D
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-44816847;