Variant 6-168030820-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030615.4(KIF25):c.140G>A(p.Cys47Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KIF25
NM_030615.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

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:

KIF25 (HGNC:):

KIF25 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.153954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF25	NM_030615.4 linkuse as main transcript	c.140G>A	p.Cys47Tyr	missense_variant	7/13	ENST00000643607.3	NP_085118.2	Q9UIL4-1
KIF25	NM_005355.5 linkuse as main transcript	c.140G>A	p.Cys47Tyr	missense_variant	7/12		NP_005346.3	Q9UIL4-2
KIF25	XM_047418749.1 linkuse as main transcript	c.140G>A	p.Cys47Tyr	missense_variant	5/11		XP_047274705.1
KIF25	XM_011535803.4 linkuse as main transcript	c.140G>A	p.Cys47Tyr	missense_variant	5/10		XP_011534105.1	Q9UIL4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF25	ENST00000643607.3 linkuse as main transcript	c.140G>A	p.Cys47Tyr	missense_variant	7/13		NM_030615.4	ENSP00000496229.1		Q9UIL4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250658

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135494

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:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460976

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Feb 15, 2023

The c.140G>A (p.C47Y) alteration is located in exon 3 (coding exon 2) of the KIF25 gene. This alteration results from a G to A substitution at nucleotide position 140, causing the cysteine (C) at amino acid position 47 to be replaced by a tyrosine (Y). 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

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.9

DANN

Benign

0.33

DEOGEN2

Benign

0.31

T;T;T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.95

.;.;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;L;L;L

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

.;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.12

.;T;T;T

Sift4G

Benign

0.11

.;T;T;T

Polyphen

0.19

B;B;B;B

Vest4

0.31, 0.37

MutPred

0.54

Gain of phosphorylation at C47 (P = 0.0857);Gain of phosphorylation at C47 (P = 0.0857);Gain of phosphorylation at C47 (P = 0.0857);Gain of phosphorylation at C47 (P = 0.0857);

MVP

0.33

MPC

0.25

ClinPred

0.13

GERP RS

0.89

Varity_R

0.16

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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