Variant 17-74344776-A-T 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_153209.4(KIF19):c.598A>T(p.Met200Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,834 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KIF19
NM_153209.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0290

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 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=0.09576133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF19	NM_153209.4 linkuse as main transcript	c.598A>T	p.Met200Leu	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.598A>T	p.Met200Leu	missense_variant	7/20	5	NM_153209.4	ENSP00000374566	P1	Q2TAC6-1
KIF19	ENST00000359939.10 linkuse as main transcript	n.591A>T		non_coding_transcript_exon_variant	6/11	1
KIF19	ENST00000547389.1 linkuse as main transcript	n.691A>T		non_coding_transcript_exon_variant	7/12	1
KIF19	ENST00000551294.5 linkuse as main transcript	c.472A>T	p.Met158Leu	missense_variant	6/13	5		ENSP00000449134

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455834

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 30, 2022

The c.598A>T (p.M200L) alteration is located in exon 7 (coding exon 7) of the KIF19 gene. This alteration results from a A to T substitution at nucleotide position 598, causing the methionine (M) at amino acid position 200 to be replaced by a leucine (L). 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

0.089

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.10

.;N

MutationTaster

Benign

0.82

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.12

Sift

Benign

0.77

T;T

Sift4G

Benign

0.98

T;T

Polyphen

0.0

B;B

Vest4

0.28

MutPred

0.47

.;Loss of helix (P = 0.028);

MVP

0.66

MPC

0.16

ClinPred

0.034

GERP RS

0.36

Varity_R

0.056

gMVP

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over