Variant chr16-57752551-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1

The NM_005886.3(KATNB1):c.654G>A(p.Leu218=) 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:5

Conservation

PhyloP100: 3.88

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KATNB1	NM_005886.3 linkuse as main transcript	c.654G>A	p.Leu218=	synonymous_variant	9/20	ENST00000379661.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KATNB1	ENST00000379661.8 linkuse as main transcript	c.654G>A	p.Leu218=	synonymous_variant	9/20	5	NM_005886.3	P1
KATNB1	ENST00000566611.5 linkuse as main transcript	n.1647G>A		non_coding_transcript_exon_variant	8/15	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

GnomAD3 exomes

AF:

0.000707

AC:

127

AN:

179522

Hom.:

AF XY:

0.000703

AC XY:

AN XY:

95364

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 SAS exome

AF:

0.000124

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

Gnomad4 AFR exome

AF:

0.000274

Gnomad4 AMR exome

AF:

0.000217

Gnomad4 ASJ exome

AF:

0.000277

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000497

Gnomad4 FIN exome

AF:

0.000322

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.000902

GnomAD4 genome

AF:

0.000807

AC:

123

AN:

152370

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000986

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 08, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	KATNB1: BP4, BP7 -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 25, 2016

- -

KATNB1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

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

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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