chr16-27594376-C-T

Variant names:

• chr16-27594376-C-T
• rs4787976
• NM_015202.5:c.63+20420C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015202.5(KATNIP):​c.63+20420C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 151,884 control chromosomes in the GnomAD database, including 49,802 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (49802 hom., cov: 30)
• Consequence: KATNIP NM_015202.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 4 publications found

Genes affected

KATNIP (HGNC:29068): (katanin interacting protein) This gene encodes a novel, evolutionarily conserved, ciliary protein. In human hTERT-RPE1 cells, the protein is found at the base of cilia, decorating the ciliary axoneme, and enriched at the ciliary tip. The protein binds to microtubules in vitro and regulates their stability when it is overexpressed. A null mutation in this gene has been associated with Joubert syndrome, a recessive disorder that is characterized by a distinctive mid-hindbrain and cerebellar malformation and is also often associated with wider ciliopathy symptoms. Consistently, in a serum-starvation ciliogenesis assay, human fibroblast cells derived from patients with the mutation display a reduced number of ciliated cells with abnormally long cilia. [provided by RefSeq, Feb 2016]

KATNIP Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 26

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015202.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNIP	NM_015202.5	MANE Select	c.63+20420C>T		intron	N/A	NP_056017.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNIP	ENST00000261588.10	TSL:1 MANE Select	c.63+20420C>T		intron	N/A	ENSP00000261588.4
	KATNIP	ENST00000568258.5	TSL:3	c.48+20420C>T		intron	N/A	ENSP00000454884.1
	KATNIP	ENST00000565672.5	TSL:3	n.33+20420C>T		intron	N/A	ENSP00000455380.1

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122657 AN: 151766 Hom.: 49766 Cov.: 30

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.818

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.808 AC: 122739 AN: 151884 Hom.: 49802 Cov.: 30 AF XY: 0.809 AC XY: 60020 AN XY: 74226

African (AFR) AF: 0.744 AC: 30787 AN: 41404

American (AMR) AF: 0.808 AC: 12324 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2772 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5108 AN: 5126

South Asian (SAS) AF: 0.932 AC: 4488 AN: 4818

European-Finnish (FIN) AF: 0.831 AC: 8759 AN: 10544

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55739 AN: 67966

Other (OTH) AF: 0.820 AC: 1726 AN: 2106

Alfa AF: 0.783 Hom.: 3867

Bravo AF: 0.803

Asia WGS AF: 0.956 AC: 3323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.72
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs4787976; hg19: chr16-27605697;