Variant 16-57765550-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001130100.2(KIFC3):c.1421A>C(p.Asp474Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D474N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

KIFC3
NM_001130100.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFC3	NM_001130100.2 linkuse as main transcript	c.1421A>C	p.Asp474Ala	missense_variant	11/20	ENST00000445690.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIFC3	ENST00000445690.7 linkuse as main transcript	c.1421A>C	p.Asp474Ala	missense_variant	11/20	1	NM_001130100.2	A1	Q9BVG8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1452196

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721366

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2023

The c.1421A>C (p.D474A) alteration is located in exon 11 (coding exon 10) of the KIFC3 gene. This alteration results from a A to C substitution at nucleotide position 1421, causing the aspartic acid (D) at amino acid position 474 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

.;T;.;.;.;.;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.071

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

.;D;D;.;D;D;D;D

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.49

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.4

.;L;L;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.0

D;D;D;D;D;D;D;D

REVEL

Uncertain

0.48

Sift

Benign

0.030

D;T;T;D;T;D;D;D

Sift4G

Benign

0.14

T;T;T;T;T;T;T;T

Polyphen

0.96, 0.083, 0.36

.;D;.;.;.;B;B;.

Vest4

0.47

MVP

0.83

MPC

1.4

ClinPred

0.92

GERP RS

5.4

Varity_R

0.38

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over