Variant 3-44784844-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_020242.3(KIF15):c.362-1G>A variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,443,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely risk allele (no stars).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

KIF15
NM_020242.3 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely risk allele no assertion criteria provided P:1

Conservation

PhyloP100: 8.89

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 Pathogenic. Variant got 11 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 8.1, offset of 1, new splice context is: ttttttttcatttttttaAGacc. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 3-44784844-G-A is Pathogenic according to our data. Variant chr3-44784844-G-A is described in ClinVar as [Likely_risk_allele]. Clinvar id is 1695969.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF15	NM_020242.3 link	c.362-1G>A		splice_acceptor_variant, intron_variant		ENST00000326047.9	NP_064627.1	Q9NS87-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
KIF15	ENST00000326047.9 link	c.362-1G>A	splice_acceptor_variant, intron_variant	1	NM_020242.3	ENSP00000324020.4	Q9NS87-1
KIF15	ENST00000438321.5 link	n.*67-1G>A	splice_acceptor_variant, intron_variant	1		ENSP00000406939.1	F8WC33
KIF15	ENST00000481166.6 link	c.-46+3922G>A	intron_variant	5		ENSP00000425499.1	D6RCT7

Frequencies

GnomAD3 genomes

AF:

0.0000467

AC:

AN:

149940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000736

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000592

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000572

AC:

AN:

209786

Hom.:

AF XY:

0.0000437

AC XY:

AN XY:

114540

show subpopulations

Gnomad AFR exome

AF:

0.0000706

Gnomad AMR exome

AF:

0.0000447

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000989

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000441

AC:

AN:

1293128

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

649978

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:

0.0000548

Gnomad4 OTH exome

AF:

0.0000554

GnomAD4 genome

AF:

0.0000467

AC:

AN:

149940

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

73004

show subpopulations

Gnomad4 AFR

AF:

0.0000736

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000592

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary fibrosis

Pathogenic:1

Likely risk allele, no assertion criteria provided

research

Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center

Jun 09, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

0.99

GERP RS

5.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.49

Position offset: 2

DS_AL_spliceai

0.97

Position offset: 1

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