KATNB1 p.Leu218Leu

Variant names:

• chr16-57752548-C-C
• NM_005886.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr16-57752549--
• chr16-57752549-C-T
• chr16-57752551-G-T
• chr16-57752551-G-C
• chr16-57752551-G-A
• chr16-57752549-CTG-TTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005886.3(KATNB1):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KATNB1 NM_005886.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.991
• Publications: 0 publications found

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: G2P, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• microlissencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNB1	NM_005886.3	MANE Select	c.		intron	N/A	NP_005877.2	Q9BVA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNB1	ENST00000379661.8	TSL:5 MANE Select	c.		splice_donor intron	N/A	ENSP00000368982.3	Q9BVA0
	KATNB1	ENST00000874409.1		c.		splice_donor intron	N/A	ENSP00000544468.1
	KATNB1	ENST00000912658.1		c.		splice_donor intron	N/A	ENSP00000582717.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-57786460;