rs730880259

Variant names:

• chr16-57741743-G-T
• rs730880259
• NM_005886.3:c.97G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-57741743-G-T
• chr16-57741743-G-A
• chr16-57741743-G-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_005886.3(KATNB1):​c.97G>T​(p.Gly33Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: KATNB1 NM_005886.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 8.04
• Publications: 4 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936
• PP5: Variant 16-57741743-G-T is Pathogenic according to our data. Variant chr16-57741743-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 180640.Status of the report is criteria_provided_single_submitter, 1 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNB1	NM_005886.3	MANE Select	c.97G>T	p.Gly33Trp	missense	Exon 3 of 20	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.97G>T	p.Gly33Trp	missense	Exon 3 of 20	ENSP00000368982.3	Q9BVA0
	KATNB1	ENST00000874409.1		c.97G>T	p.Gly33Trp	missense	Exon 3 of 20	ENSP00000544468.1
	KATNB1	ENST00000912658.1		c.97G>T	p.Gly33Trp	missense	Exon 3 of 20	ENSP00000582717.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Lissencephaly 6 with microcephaly (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.73	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		8.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.75		Gain of MoRF binding (P = 0.0219)
MVP		0.87
MPC		1.5
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.92
gMVP		0.64
Mutation Taster		=12/88	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs730880259; hg19: chr16-57775655; COSMIC: COSV65560188;