Variant 6-33403344-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002263.4(KIFC1):c.281G>A(p.Arg94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

KIFC1
NM_002263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

KIFC1 (HGNC:6389): (kinesin family member C1) Predicted to enable microtubule binding activity and minus-end-directed microtubule motor activity. Involved in mitotic metaphase plate congression and mitotic spindle assembly. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIFC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044569314).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KIFC1	NM_002263.4 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/11	ENST00000428849.7	NP_002254.2
KIFC1	XM_011514585.2 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/12		XP_011512887.1
KIFC1	XM_017010837.2 linkuse as main transcript	c.158G>A	p.Arg53Gln	missense_variant	4/11		XP_016866326.2
KIFC1	XM_011514587.3 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/10		XP_011512889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KIFC1	ENST00000428849.7 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/11	1	NM_002263.4	ENSP00000393963	P1
KIFC1	ENST00000450504.1 linkuse as main transcript	c.404G>A	p.Arg135Gln	missense_variant	5/7	3		ENSP00000409539
KIFC1	ENST00000486695.1 linkuse as main transcript	n.455G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000187

AC:

AN:

251492

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.0000972

AC:

142

AN:

1461650

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000117

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Mar 31, 2024

The c.281G>A (p.R94Q) alteration is located in exon 4 (coding exon 4) of the KIFC1 gene. This alteration results from a G to A substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 to be replaced by a glutamine (Q). 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

0.078

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.026

T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.17

N;N

REVEL

Benign

0.15

Sift

Benign

0.20

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.97

D;.

Vest4

0.17

MVP

0.79

MPC

0.54

ClinPred

0.065

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.077

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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