chr6-168033981-C-A

Position:

chr6-168033981-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_030615.4(KIF25):c.267C>A(p.Asp89Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

KIF25
NM_030615.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.272

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_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017964095).

BP6

Variant 6-168033981-C-A is Benign according to our data. Variant chr6-168033981-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3288551.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KIF25	NM_030615.4 linkuse as main transcript	c.267C>A	p.Asp89Glu	missense_variant	8/13	ENST00000643607.3	NP_085118.2
KIF25	NM_005355.5 linkuse as main transcript	c.267C>A	p.Asp89Glu	missense_variant	8/12		NP_005346.3
KIF25	XM_047418749.1 linkuse as main transcript	c.267C>A	p.Asp89Glu	missense_variant	6/11		XP_047274705.1
KIF25	XM_011535803.4 linkuse as main transcript	c.267C>A	p.Asp89Glu	missense_variant	6/10		XP_011534105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF25	ENST00000643607.3 linkuse as main transcript	c.267C>A	p.Asp89Glu	missense_variant	8/13		NM_030615.4	ENSP00000496229	P1	Q9UIL4-1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000705

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251442

Hom.:

AF XY:

0.000331

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000756

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000287

AC:

420

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000275

AC XY:

200

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.000331

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000381

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000705

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000413

Hom.:

Bravo

AF:

0.000280

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000511

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 26, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.0040

DANN

Benign

0.27

DEOGEN2

Benign

0.047

T;T;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.32

.;.;T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.045

N;N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.080

.;N;N;N

REVEL

Benign

0.087

Sift

Benign

0.82

.;T;T;T

Sift4G

Benign

1.0

.;T;T;T

Polyphen

0.0080

B;B;B;B

Vest4

0.10, 0.10, 0.12

MutPred

0.38

Gain of catalytic residue at D89 (P = 0.037);Gain of catalytic residue at D89 (P = 0.037);Gain of catalytic residue at D89 (P = 0.037);Gain of catalytic residue at D89 (P = 0.037);

MVP

0.24

MPC

0.096

ClinPred

0.025

GERP RS

-8.4

Varity_R

0.022

gMVP

0.11

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

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