rs200584307

Positions:

• chr16-57753072-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005886.3(KATNB1):​c.856-5T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,598,136 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (43 hom.)
• Consequence: KATNB1 NM_005886.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.06216
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.182

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-57753072-T-G is Benign according to our data. Variant chr16-57753072-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 435544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57753072-T-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00483 (736/152292) while in subpopulation NFE AF= 0.00779 (530/68006). AF 95% confidence interval is 0.00724. There are 5 homozygotes in gnomad4. There are 315 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KATNB1	NM_005886.3	c.856-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000379661.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KATNB1	ENST00000379661.8	c.856-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_005886.3	P1
KATNB1	ENST00000566611.5	n.2168T>G		non_coding_transcript_exon_variant	8/15	2

Frequencies

GnomAD3 genomes AF: 0.00484 AC: 736 AN: 152174 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00779

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00486 AC: 1173 AN: 241452 Hom.: 7 AF XY: 0.00494 AC XY: 649 AN XY: 131388

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00589

Gnomad ASJ exome AF: 0.00746

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000666

Gnomad FIN exome AF: 0.000404

Gnomad NFE exome AF: 0.00734

Gnomad OTH exome AF: 0.00774

GnomAD4 exome AF: 0.00675 AC: 9756 AN: 1445844 Hom.: 43 Cov.: 36 AF XY: 0.00658 AC XY: 4721 AN XY: 717664

Gnomad4 AFR exome AF: 0.00147

Gnomad4 AMR exome AF: 0.00679

Gnomad4 ASJ exome AF: 0.00624

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00100

Gnomad4 FIN exome AF: 0.000627

Gnomad4 NFE exome AF: 0.00781

Gnomad4 OTH exome AF: 0.00789

GnomAD4 genome AF: 0.00483 AC: 736 AN: 152292 Hom.: 5 Cov.: 33 AF XY: 0.00423 AC XY: 315 AN XY: 74464

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00779

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00618 Hom.: 1

Bravo AF: 0.00547

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	KATNB1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 01, 2016

- -

KATNB1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 30, 2019

This variant is classified as 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	-0.59
CADD	Benign	7.7
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.062
dbscSNV1_RF	Benign	0.18
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

LitVar

Other links and lift over

dbSNP: rs200584307; hg19: chr16-57786984;