Genetic Variant NM_001130100.2:c.2324G>T (chr16-57760325-C-A) – 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>T(p.Arg775Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 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: 0.0000021 ( 0 hom. )

Consequence

KIFC3
NM_001130100.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.23

Publications

0 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:

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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, 0.763

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>T	p.Arg775Leu	missense	Exon 17 of 20	NP_001123572.1	Q9BVG8-2
KIFC3	NM_001318710.2		c.2390G>T	p.Arg797Leu	missense	Exon 17 of 20	NP_001305639.1	Q9BVG8-6
KIFC3	NM_005550.4		c.2324G>T	p.Arg775Leu	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>T	p.Arg775Leu	missense	Exon 17 of 20	ENSP00000401696.2	Q9BVG8-2
KIFC3	ENST00000379655.8	TSL:1	c.2324G>T	p.Arg775Leu	missense	Exon 17 of 19	ENSP00000368976.4	Q9BVG8-3
KIFC3	ENST00000465878.6	TSL:1	c.1907G>T	p.Arg636Leu	missense	Exon 17 of 20	ENSP00000454659.1	Q9BVG8-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461558

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.00

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:

0.00000270

AC:

AN:

1111940

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.76

MetaSVM

Uncertain

0.082

MutationAssessor

Benign

1.4

PhyloP100

5.2

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.60

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.79

MutPred

0.52

Loss of MoRF binding (P = 0.0358)

MVP

0.89

MPC

1.6

ClinPred

1.0

GERP RS

5.2

Varity_R

0.71

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over