Variant 17-74344842-G-A 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_153209.4(KIF19):c.664G>A(p.Ala222Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00224 in 1,612,806 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 6 hom. )

Consequence

KIF19
NM_153209.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.48

Variant links:

Genes affected

KIF19 (HGNC:26735): (kinesin family member 19) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in axonemal microtubule depolymerization; microtubule-based movement; and plus-end specific microtubule depolymerization. Predicted to be located in cilium. Predicted to be part of kinesin complex. Predicted to be active in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

KIF19 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=0.035112053).

BP6

Variant 17-74344842-G-A is Benign according to our data. Variant chr17-74344842-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 711078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF19	NM_153209.4 linkuse as main transcript	c.664G>A	p.Ala222Thr	missense_variant	7/20	ENST00000389916.5	NP_694941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF19	ENST00000389916.5 linkuse as main transcript	c.664G>A	p.Ala222Thr	missense_variant	7/20	5	NM_153209.4	ENSP00000374566	P1	Q2TAC6-1
KIF19	ENST00000359939.10 linkuse as main transcript	n.657G>A		non_coding_transcript_exon_variant	6/11	1
KIF19	ENST00000547389.1 linkuse as main transcript	n.757G>A		non_coding_transcript_exon_variant	7/12	1
KIF19	ENST00000551294.5 linkuse as main transcript	c.538G>A	p.Ala180Thr	missense_variant	6/13	5		ENSP00000449134

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

291

AN:

152276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00413

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00244

AC:

609

AN:

249132

Hom.:

AF XY:

0.00260

AC XY:

352

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00491

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00425

Gnomad FIN exome

AF:

0.000602

Gnomad NFE exome

AF:

0.00297

Gnomad OTH exome

AF:

0.00263

GnomAD4 exome

AF:

0.00228

AC:

3323

AN:

1460412

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1746

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00456

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00466

Gnomad4 FIN exome

AF:

0.000956

Gnomad4 NFE exome

AF:

0.00222

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.00192

AC:

292

AN:

152394

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.000288

Gnomad4 AMR

AF:

0.00300

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00307

Hom.:

Bravo

AF:

0.00158

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00257

AC:

312

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00290

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	KIF19: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

.;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

T;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.035

T;T

MetaSVM

Uncertain

0.099

MutationAssessor

Benign

2.0

.;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.0

D;D

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.62

MVP

0.90

MPC

0.68

ClinPred

0.036

GERP RS

5.5

Varity_R

0.53

gMVP

0.54

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