Genetic Variant KIFC3:p.Arg775Pro (chr16-57760325-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001130100.2(KIFC3):c.2324G>C(p.Arg775Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R775H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KIFC3
NM_001130100.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.23

Publications

1 publications found

Variant links:

Genes affected

KIFC3 (HGNC:6326): (kinesin family member C3) This gene encodes a member of the kinesin-14 family of microtubule motors. Members of this family play a role in the formation, maintenance and remodeling of the bipolar mitotic spindle. The protein encoded by this gene has cytoplasmic functions in the interphase cells. It may also be involved in the final stages of cytokinesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

KIFC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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, 0.773

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130100.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIFC3	NM_001130100.2	MANE Select	c.2324G>C	p.Arg775Pro	missense	Exon 17 of 20	NP_001123572.1	Q9BVG8-2
KIFC3	NM_001318710.2		c.2390G>C	p.Arg797Pro	missense	Exon 17 of 20	NP_001305639.1	Q9BVG8-6
KIFC3	NM_005550.4		c.2324G>C	p.Arg775Pro	missense	Exon 17 of 19	NP_005541.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIFC3	ENST00000445690.7	TSL:1 MANE Select	c.2324G>C	p.Arg775Pro	missense	Exon 17 of 20	ENSP00000401696.2	Q9BVG8-2
KIFC3	ENST00000379655.8	TSL:1	c.2324G>C	p.Arg775Pro	missense	Exon 17 of 19	ENSP00000368976.4	Q9BVG8-3
KIFC3	ENST00000465878.6	TSL:1	c.1907G>C	p.Arg636Pro	missense	Exon 17 of 20	ENSP00000454659.1	Q9BVG8-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251048

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461558

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111940

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

0.089

MutationAssessor

Benign

1.4

PhyloP100

5.2

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.3

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.80

MutPred

0.56

Loss of MoRF binding (P = 0.0109)

MVP

0.95

MPC

1.8

ClinPred

0.99

GERP RS

5.2

Varity_R

0.80

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over