Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_005886.3(KATNB1):c.1A>G(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

KATNB1
NM_005886.3 start_lost

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.17

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 4 pathogenic variants. Next in-frame start position is after 57 codons. Genomic position: 57741815. Lost 0.086 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 16-57737244-A-G is Pathogenic according to our data. Variant chr16-57737244-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 180639.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005886.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNB1	NM_005886.3	MANE Select	c.1A>G	p.Met1?	start_lost	Exon 2 of 20	NP_005877.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KATNB1	ENST00000379661.8	TSL:5 MANE Select	c.1A>G	p.Met1?	start_lost	Exon 2 of 20	ENSP00000368982.3
KATNB1	ENST00000562592.5	TSL:3	c.1A>G	p.Met1?	start_lost	Exon 3 of 9	ENSP00000455350.1
KATNB1	ENST00000569627.1	TSL:3	c.1A>G	p.Met1?	start_lost	Exon 1 of 5	ENSP00000457046.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Lissencephaly 6 with microcephaly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.83

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-0.57

PhyloP100

6.2

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.71

Vest4

0.93

MutPred

0.89

Loss of MoRF binding (P = 0.0923)

MVP

0.74

ClinPred

1.0

GERP RS

5.0

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.50

Mutation Taster

=2/198

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs879255518

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over