rs200584307

Variant names:

• chr16-57753072-T-G
• rs200584307
• NM_005886.3:c.856-5T>G

Variant summary

Our verdict is Benign. The variant received -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, 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, intron
• Scores: Splicing: ADA: 0.06216
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.182
• Publications: 1 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 435544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.856-5T>G		splice_region 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.856-5T>G		splice_region intron	N/A	ENSP00000368982.3	Q9BVA0
	KATNB1	ENST00000874409.1		c.856-5T>G		splice_region intron	N/A	ENSP00000544468.1
	KATNB1	ENST00000912658.1		c.856-5T>G		splice_region intron	N/A	ENSP00000582717.1

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

GnomAD2 exomes AF: 0.00486 AC: 1173 AN: 241452 AF XY: 0.00494

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 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

African (AFR) AF: 0.00147 AC: 49 AN: 33274

American (AMR) AF: 0.00679 AC: 300 AN: 44204

Ashkenazi Jewish (ASJ) AF: 0.00624 AC: 160 AN: 25628

East Asian (EAS) AF: 0.00 AC: 0 AN: 39448

South Asian (SAS) AF: 0.00100 AC: 86 AN: 85696

European-Finnish (FIN) AF: 0.000627 AC: 30 AN: 47832

Middle Eastern (MID) AF: 0.00595 AC: 34 AN: 5718

European-Non Finnish (NFE) AF: 0.00781 AC: 8625 AN: 1104184

Other (OTH) AF: 0.00789 AC: 472 AN: 59860

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

African (AFR) AF: 0.00161 AC: 67 AN: 41574

American (AMR) AF: 0.00582 AC: 89 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00779 AC: 530 AN: 68006

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00618 Hom.: 1

Bravo AF: 0.00547

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	KATNB1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.7
DANN	Benign	0.61
PhyloP100		-0.18
PromoterAI		0.060	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200584307; hg19: chr16-57786984;