rs200584307

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005886.3(KATNB1):c.856-5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,598,136 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 43 hom. )

Consequence

KATNB1
NM_005886.3 splice_region, intron

Scores

Splicing: ADA: 0.06216

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.182

Publications

1 publications found

Variant links:

Genes affected

KATNB1 (HGNC:6217): (katanin regulatory subunit B1) Microtubules, polymers of alpha and beta tubulin subunits, form the mitotic spindle of a dividing cell and help to organize membranous organelles during interphase. Katanin is a heterodimer that consists of a 60 kDa ATPase (p60 subunit A 1) and an 80 kDa accessory protein (p80 subunit B 1). The p60 subunit acts to sever and disassemble microtubules, while the p80 subunit targets the enzyme to the centrosome. Katanin is a member of the AAA family of ATPases. [provided by RefSeq, Jul 2008]

KATNB1 Gene-Disease associations (from GenCC):

lissencephaly 6 with microcephaly
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, G2P
microlissencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KATNB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 16-57753072-T-G is Benign according to our data. Variant chr16-57753072-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 435544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00483 (736/152292) while in subpopulation NFE AF = 0.00779 (530/68006). AF 95% confidence interval is 0.00724. There are 5 homozygotes in GnomAd4. There are 315 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNB1	NM_005886.3 link	c.856-5T>G		splice_region_variant, intron_variant	Intron 10 of 19	ENST00000379661.8	NP_005877.2	Q9BVA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNB1	ENST00000379661.8 link	c.856-5T>G		splice_region_variant, intron_variant	Intron 10 of 19	5	NM_005886.3	ENSP00000368982.3		Q9BVA0
KATNB1	ENST00000566611.5 link	n.2168T>G		non_coding_transcript_exon_variant	Exon 8 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.00484

AC:

736

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00779

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00486

AC:

1173

AN:

241452

AF XY:

0.00494

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00589

Gnomad ASJ exome

AF:

0.00746

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000404

Gnomad NFE exome

AF:

0.00734

Gnomad OTH exome

AF:

0.00774

GnomAD4 exome

AF:

0.00675

AC:

9756

AN:

1445844

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

4721

AN XY:

717664

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

33274

American (AMR)

AF:

0.00679

AC:

300

AN:

44204

Ashkenazi Jewish (ASJ)

AF:

0.00624

AC:

160

AN:

25628

East Asian (EAS)

AF:

0.00

AC:

AN:

39448

South Asian (SAS)

AF:

0.00100

AC:

AN:

85696

European-Finnish (FIN)

AF:

0.000627

AC:

AN:

47832

Middle Eastern (MID)

AF:

0.00595

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00781

AC:

8625

AN:

1104184

Other (OTH)

AF:

0.00789

AC:

472

AN:

59860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

505

1011

1516

2022

2527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

318

636

954

1272

1590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00483

AC:

736

AN:

152292

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

315

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41574

American (AMR)

AF:

0.00582

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00779

AC:

530

AN:

68006

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

113

151

189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00618

Hom.:

Bravo

AF:

0.00547

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KATNB1: BP4, BS2 -

Dec 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Dec 01, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

KATNB1-related disorder

Benign:1

Dec 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.7

(source)

DANN

Benign

0.61

PhyloP100

-0.18

PromoterAI

0.060

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.062

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over