chr16-57752551-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS1

The NM_005886.3(KATNB1):c.654G>A(p.Leu218Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00118 in 1,568,690 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

KATNB1
NM_005886.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.88

Publications

2 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 16-57752551-G-A is Benign according to our data. Variant chr16-57752551-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435543.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 = 0.000807 (123/152370) while in subpopulation NFE AF = 0.00154 (105/68026). AF 95% confidence interval is 0.0013. There are 0 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNB1	NM_005886.3 link	c.654G>A	p.Leu218Leu	synonymous_variant	Exon 9 of 20	ENST00000379661.8	NP_005877.2	Q9BVA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNB1	ENST00000379661.8 link	c.654G>A	p.Leu218Leu	synonymous_variant	Exon 9 of 20	5	NM_005886.3	ENSP00000368982.3		Q9BVA0
KATNB1	ENST00000566611.5 link	n.1647G>A		non_coding_transcript_exon_variant	Exon 8 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.000808

AC:

123

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000707

AC:

127

AN:

179522

AF XY:

0.000703

show subpopulations

Gnomad AFR exome

AF:

0.000546

Gnomad AMR exome

AF:

0.000115

Gnomad ASJ exome

AF:

0.000230

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000311

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00122

AC:

1734

AN:

1416320

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

807

AN XY:

699984

show subpopulations

African (AFR)

AF:

0.000274

AC:

AN:

32892

American (AMR)

AF:

0.000217

AC:

AN:

36898

Ashkenazi Jewish (ASJ)

AF:

0.000277

AC:

AN:

25246

East Asian (EAS)

AF:

0.00

AC:

AN:

38014

South Asian (SAS)

AF:

0.0000497

AC:

AN:

80540

European-Finnish (FIN)

AF:

0.000322

AC:

AN:

49672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00150

AC:

1637

AN:

1088606

Other (OTH)

AF:

0.000902

AC:

AN:

58740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000807

AC:

123

AN:

152370

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41588

American (AMR)

AF:

0.000457

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00154

AC:

105

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000986

ClinVar

Significance: Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KATNB1: BP4, BP7 -

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 22, 2020

GeneDx

Significance:Likely 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

Jul 25, 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

Apr 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

-0.41

CADD

Benign

9.6

(source)

DANN

Benign

0.77

PhyloP100

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

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chr16-57752551-G-A

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