Variant 6-168040096-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030615.4(KIF25):c.526C>T(p.Leu176Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KIF25
NM_030615.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

KIF25 (HGNC:6390): (kinesin family member 25) The protein encoded by this gene is a member of the kinesin-like protein family. Protein family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. However, the particular function of this gene product has not yet been determined. Two alternatively spliced transcript variants which encode products have been described. Other splice variants have been found that lack exon 2 and the initiation codon for translation. [provided by RefSeq, Jul 2008]

KIF25 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF25	NM_030615.4 link	c.526C>T	p.Leu176Phe	missense_variant	10/13	ENST00000643607.3	NP_085118.2	Q9UIL4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIF25	ENST00000643607.3 link	c.526C>T	p.Leu176Phe	missense_variant	10/13		NM_030615.4	ENSP00000496229.1	Q9UIL4-1
KIF25	ENST00000443060.6 link	c.526C>T	p.Leu176Phe	missense_variant	7/10	5		ENSP00000388878.2	Q9UIL4-1
KIF25	ENST00000644536.1 link	n.788C>T		non_coding_transcript_exon_variant	6/9
KIF25	ENST00000645382.1 link	n.760C>T		non_coding_transcript_exon_variant	6/8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461436

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 12, 2024

The c.526C>T (p.L176F) alteration is located in exon 6 (coding exon 5) of the KIF25 gene. This alteration results from a C to T substitution at nucleotide position 526, causing the leucine (L) at amino acid position 176 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T;T;.

Eigen

Benign

-0.025

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.54

.;.;T;T

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.73

D;D;D;D

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.2

M;M;M;M

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.6

.;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.011

.;D;D;D

Sift4G

Uncertain

0.017

.;D;D;D

Polyphen

0.88

P;P;P;D

Vest4

0.53, 0.53, 0.56

MutPred

0.72

Loss of stability (P = 0.1035);Loss of stability (P = 0.1035);Loss of stability (P = 0.1035);Loss of stability (P = 0.1035);

MVP

0.67

MPC

0.42

ClinPred

0.74

GERP RS

2.2

Varity_R

0.50

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over