Variant 3-44786567-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020242.3(KIF15):c.632C>T(p.Ala211Val) variant causes a missense change. The variant allele was found at a frequency of 0.0032 in 1,609,804 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0024 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 13 hom. )

Consequence

KIF15
NM_020242.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

KIF15 (HGNC:17273): (kinesin family member 15) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIF15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012339711).

BP6

Variant 3-44786567-C-T is Benign according to our data. Variant chr3-44786567-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 717832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF15	NM_020242.3 linkuse as main transcript	c.632C>T	p.Ala211Val	missense_variant	7/35	ENST00000326047.9	NP_064627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF15	ENST00000326047.9 linkuse as main transcript	c.632C>T	p.Ala211Val	missense_variant	7/35	1	NM_020242.3	ENSP00000324020	P1	Q9NS87-1
KIF15	ENST00000438321.5 linkuse as main transcript	c.*337C>T		3_prime_UTR_variant, NMD_transcript_variant	6/34	1		ENSP00000406939
KIF15	ENST00000481166.6 linkuse as main transcript	c.-46+5645C>T		intron_variant		5		ENSP00000425499

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

365

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00370

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00323

AC:

810

AN:

250480

Hom.:

AF XY:

0.00347

AC XY:

470

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00473

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.00463

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00328

AC:

4781

AN:

1457548

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

2461

AN XY:

724656

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.00239

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00426

Gnomad4 FIN exome

AF:

0.00193

Gnomad4 NFE exome

AF:

0.00354

Gnomad4 OTH exome

AF:

0.00319

GnomAD4 genome

AF:

0.00241

AC:

367

AN:

152256

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00371

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00362

Hom.:

Bravo

AF:

0.00221

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00359

AC:

436

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.091

Eigen

Benign

-0.026

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.015

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.045

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.78

REVEL

Benign

0.20

Sift

Benign

0.14

Sift4G

Uncertain

0.0080

Polyphen

0.50

Vest4

0.46

MVP

0.68

MPC

0.23

ClinPred

0.026

GERP RS

5.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.25

gMVP

0.48

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