Variant 6-168034009-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_030615.4(KIF25):c.295A>G(p.Arg99Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KIF25
NM_030615.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF25	NM_030615.4 link	c.295A>G	p.Arg99Gly	missense_variant	8/13	ENST00000643607.3	NP_085118.2	Q9UIL4-1
KIF25	NM_005355.5 link	c.295A>G	p.Arg99Gly	missense_variant	8/12		NP_005346.3	Q9UIL4-2
KIF25	XM_047418749.1 link	c.295A>G	p.Arg99Gly	missense_variant	6/11		XP_047274705.1
KIF25	XM_011535803.4 link	c.295A>G	p.Arg99Gly	missense_variant	6/10		XP_011534105.1	Q9UIL4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF25	ENST00000643607.3 link	c.295A>G	p.Arg99Gly	missense_variant	8/13		NM_030615.4	ENSP00000496229.1		Q9UIL4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

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:

0.0000232

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

Dec 19, 2022

The c.295A>G (p.R99G) alteration is located in exon 4 (coding exon 3) of the KIF25 gene. This alteration results from a A to G substitution at nucleotide position 295, causing the arginine (R) at amino acid position 99 to be replaced by a glycine (G). 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

0.22

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Uncertain

0.63

D;D;D;.

Eigen

Benign

0.18

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

.;.;D;D

M_CAP

Benign

0.045

MetaRNN

Pathogenic

0.98

D;D;D;D

MetaSVM

Uncertain

-0.12

MutationAssessor

Pathogenic

3.0

M;M;M;M

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.0

.;D;D;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0020

.;D;D;D

Sift4G

Uncertain

0.0030

.;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.75, 0.74

MutPred

0.88

Gain of catalytic residue at V100 (P = 0.1294);Gain of catalytic residue at V100 (P = 0.1294);Gain of catalytic residue at V100 (P = 0.1294);Gain of catalytic residue at V100 (P = 0.1294);

MVP

0.73

MPC

0.56

ClinPred

0.99

GERP RS

1.6

Varity_R

0.85

gMVP

0.73

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