Variant 6-168030801-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_030615.4(KIF25):c.121G>A(p.Ala41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,613,026 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.018 ( 93 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 97 hom. )

Consequence

KIF25
NM_030615.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.112

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003274113).

BP6

Variant 6-168030801-G-A is Benign according to our data. Variant chr6-168030801-G-A is described in ClinVar as [Benign]. Clinvar id is 776185.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF25	NM_030615.4 link	c.121G>A	p.Ala41Thr	missense_variant	7/13	ENST00000643607.3	NP_085118.2	Q9UIL4-1
KIF25	NM_005355.5 link	c.121G>A	p.Ala41Thr	missense_variant	7/12		NP_005346.3	Q9UIL4-2
KIF25	XM_047418749.1 link	c.121G>A	p.Ala41Thr	missense_variant	5/11		XP_047274705.1
KIF25	XM_011535803.4 link	c.121G>A	p.Ala41Thr	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 link	c.121G>A	p.Ala41Thr	missense_variant	7/13		NM_030615.4	ENSP00000496229.1		Q9UIL4-1

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2758

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00510

AC:

1276

AN:

250318

Hom.:

AF XY:

0.00366

AC XY:

496

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.0668

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00211

AC:

3079

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1359

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.0693

Gnomad4 AMR exome

AF:

0.00305

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.000404

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.00482

GnomAD4 genome

AF:

0.0182

AC:

2768

AN:

152180

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1327

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0629

Gnomad4 AMR

AF:

0.00596

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00344

Hom.:

Bravo

AF:

0.0211

ESP6500AA

AF:

0.0656

AC:

289

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00637

AC:

774

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000416

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.2

DANN

Benign

0.86

DEOGEN2

Benign

0.056

T;T;T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.56

.;.;T;T

MetaRNN

Benign

0.0033

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.14

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

.;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.40

.;T;T;T

Sift4G

Benign

0.57

.;T;T;T

Polyphen

0.74

P;P;P;P

Vest4

0.12, 0.12, 0.21

MVP

0.51

MPC

0.11

ClinPred

0.0052

GERP RS

-0.56

Varity_R

0.058

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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