Variant 15-40594355-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144508.5(KNL1):c.-55G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 152,346 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 424 hom., cov: 33)

Exomes 𝑓: 0.093 ( 0 hom. )

Consequence

KNL1
NM_144508.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.199

Variant links:

Genes affected

KNL1 (HGNC:24054): (kinetochore scaffold 1) The protein encoded by this gene is a component of the multiprotein assembly that is required for creation of kinetochore-microtubule attachments and chromosome segregation. The encoded protein functions as a scaffold for proteins that influence the spindle assembly checkpoint during the eukaryotic cell cycle and it interacts with at least five different kinetochore proteins and two checkpoint kinases. In adults, this gene is predominantly expressed in normal testes, various cancer cell lines and primary tumors from other tissues and is ubiquitously expressed in fetal tissues. This gene was originally identified as a fusion partner with the mixed-lineage leukemia (MLL) gene in t(11;15)(q23;q14). Mutations in this gene cause autosomal recessive primary microcephaly-4 (MCPH4). Alternative splicing results in multiple transcript variants encoding different isoforms. Additional splice variants have been described but their biological validity has not been confirmed. [provided by RefSeq, Jan 2013]

KNL1 links:

KNL1 (HGNC:):

KNL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 15-40594355-G-A is Benign according to our data. Variant chr15-40594355-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 315839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KNL1	NM_144508.5 linkuse as main transcript	c.-55G>A		5_prime_UTR_variant	1/26	ENST00000399668.7	NP_653091.3	Q8NG31-2
KNL1	NM_170589.5 linkuse as main transcript	c.-55G>A		5_prime_UTR_variant	1/27		NP_733468.3	Q8NG31-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KNL1	ENST00000399668 linkuse as main transcript	c.-55G>A		5_prime_UTR_variant	1/26	1	NM_144508.5	ENSP00000382576.3		Q8NG31-2

Frequencies

GnomAD3 genomes

AF:

0.0640

AC:

9739

AN:

152174

Hom.:

424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0689

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0377

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0853

Gnomad OTH

AF:

0.0721

GnomAD4 exome

AF:

0.0926

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0909

AC XY:

AN XY:

show subpopulations

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0639

AC:

9738

AN:

152292

Hom.:

424

Cov.:

AF XY:

0.0655

AC XY:

4882

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.0688

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0379

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.0853

Gnomad4 OTH

AF:

0.0718

Alfa

AF:

0.0822

Hom.:

497

Bravo

AF:

0.0577

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary Microcephaly, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.7

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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