Variant 6-33398092-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_002263.4(KIFC1):c.76T>A(p.Ser26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,940 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

KIFC1
NM_002263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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 Likely_benign. Variant got -4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity KIFC1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.20793405).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFC1	NM_002263.4 linkuse as main transcript	c.76T>A	p.Ser26Thr	missense_variant	2/11	ENST00000428849.7	NP_002254.2	Q9BW19A0A024RCS7
KIFC1	XM_011514585.2 linkuse as main transcript	c.76T>A	p.Ser26Thr	missense_variant	2/12		XP_011512887.1
KIFC1	XM_011514587.3 linkuse as main transcript	c.76T>A	p.Ser26Thr	missense_variant	2/10		XP_011512889.1
KIFC1	XM_017010837.2 linkuse as main transcript	c.-48T>A		5_prime_UTR_variant	2/11		XP_016866326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIFC1	ENST00000428849.7 linkuse as main transcript	c.76T>A	p.Ser26Thr	missense_variant	2/11	1	NM_002263.4	ENSP00000393963.2		Q9BW19
KIFC1	ENST00000450504.1 linkuse as main transcript	c.76T>A	p.Ser26Thr	missense_variant	2/7	3		ENSP00000409539.1		A2AB20

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251392

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000140

AC:

204

AN:

1461808

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

727206

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000198

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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 24, 2024

The c.76T>A (p.S26T) alteration is located in exon 2 (coding exon 2) of the KIFC1 gene. This alteration results from a T to A substitution at nucleotide position 76, causing the serine (S) at amino acid position 26 to be replaced by a threonine (T). 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

0.089

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.093

T;.

Eigen

Benign

0.053

Eigen_PC

Benign

0.073

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.56

.;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.11

T;D

Polyphen

0.88

P;.

Vest4

0.38

MutPred

0.17

Gain of glycosylation at S26 (P = 0.0191);Gain of glycosylation at S26 (P = 0.0191);

MVP

0.77

MPC

1.1

ClinPred

0.52

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.037

gMVP

0.33

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