16-57736820-C-T

Position:

• chr16-57736820-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005886.3(KATNB1):​c.-266-158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 380,922 control chromosomes in the GnomAD database, including 1,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (437 hom., cov: 33)
  • Exomes 𝑓: 0.032 (664 hom.)
• Consequence: KATNB1 NM_005886.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.111

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-57736820-C-T is Benign according to our data. Variant chr16-57736820-C-T is described in ClinVar as [Benign]. Clinvar id is 1289729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNB1	NM_005886.3	c.-266-158C>T		intron_variant		ENST00000379661.8	NP_005877.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNB1	ENST00000379661.8	c.-266-158C>T		intron_variant		5	NM_005886.3	ENSP00000368982.3

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6807 AN: 152116 Hom.: 437 Cov.: 33

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00362

Gnomad OTH AF: 0.0479

GnomAD4 exome AF: 0.0319 AC: 7288 AN: 228688 Hom.: 664 Cov.: 0 AF XY: 0.0297 AC XY: 3703 AN XY: 124860

Gnomad4 AFR exome AF: 0.0546

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.00569

Gnomad4 EAS exome AF: 0.257

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.0242

Gnomad4 NFE exome AF: 0.00322

Gnomad4 OTH exome AF: 0.0295

GnomAD4 genome AF: 0.0447 AC: 6809 AN: 152234 Hom.: 437 Cov.: 33 AF XY: 0.0493 AC XY: 3672 AN XY: 74438

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.0239

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.00362

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0174 Hom.: 25

Bravo AF: 0.0573

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs874993; hg19: chr16-57770732;