chr16-57744439-A-G

Position:

chr16-57744439-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_005886.3(KATNB1):c.217A>G(p.Thr73Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,613,414 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

KATNB1
NM_005886.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.91

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 -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0054061115).

BP6

Variant 16-57744439-A-G is Benign according to our data. Variant chr16-57744439-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 435541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57744439-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00161 (244/151762) while in subpopulation AFR AF= 0.00561 (232/41328). AF 95% confidence interval is 0.00502. There are 0 homozygotes in gnomad4. There are 102 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.217A>G	p.Thr73Ala	missense_variant	4/20	ENST00000379661.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KATNB1	ENST00000379661.8 linkuse as main transcript	c.217A>G	p.Thr73Ala	missense_variant	4/20	5	NM_005886.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

244

AN:

151644

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00563

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000486

AC:

122

AN:

251030

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.000202

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:

0.00000880

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000177

AC:

258

AN:

1461652

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

110

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00651

Gnomad4 AMR exome

AF:

0.000313

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:

0.00000540

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.00161

AC:

244

AN:

151762

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

102

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.00561

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.00197

ESP6500AA

AF:

0.00660

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000494

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 16, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 20, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 13, 2016

- -

KATNB1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 03, 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

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0066

T;T;T;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.073

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.57

T;T;T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0054

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

N;.;.;.;.

MutationTaster

Benign

0.72

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.22

N;N;N;N;N

REVEL

Benign

0.068

Sift

Benign

0.48

T;T;T;T;T

Sift4G

Benign

0.94

T;T;T;T;T

Polyphen

0.0010

B;.;.;.;.

Vest4

0.30

MVP

0.59

MPC

0.48

ClinPred

0.0085

GERP RS

5.5

Varity_R

0.033

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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