NM_015202.5:c.7+86G>A

Variant names:

• chr16-27550263-G-A
• rs4787969
• NM_015202.5:c.7+86G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015202.5(KATNIP):​c.7+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 1,486,134 control chromosomes in the GnomAD database, including 543,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52659 hom., cov: 32)
  • Exomes 𝑓: 0.86 (491113 hom.)
• Consequence: KATNIP NM_015202.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.468
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-27550263-G-A is Benign according to our data. Variant chr16-27550263-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNIP	NM_015202.5	MANE Select	c.7+86G>A		intron	N/A	NP_056017.4	O60303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNIP	ENST00000261588.10	TSL:1 MANE Select	c.7+86G>A		intron	N/A	ENSP00000261588.4	O60303
	KATNIP	ENST00000862512.1		c.7+86G>A		intron	N/A	ENSP00000532571.1
	KATNIP	ENST00000566023.1	TSL:3	n.45+86G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126264 AN: 152032 Hom.: 52623 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.827

GnomAD4 exome AF: 0.857 AC: 1143445 AN: 1333984 Hom.: 491113 AF XY: 0.859 AC XY: 566332 AN XY: 658946

African (AFR) AF: 0.758 AC: 23119 AN: 30500

American (AMR) AF: 0.827 AC: 29539 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 17250 AN: 21646

East Asian (EAS) AF: 0.999 AC: 38412 AN: 38468

South Asian (SAS) AF: 0.935 AC: 71952 AN: 76942

European-Finnish (FIN) AF: 0.881 AC: 44877 AN: 50956

Middle Eastern (MID) AF: 0.819 AC: 4373 AN: 5338

European-Non Finnish (NFE) AF: 0.851 AC: 867056 AN: 1019210

Other (OTH) AF: 0.849 AC: 46867 AN: 55220

GnomAD4 genome AF: 0.830 AC: 126348 AN: 152150 Hom.: 52659 Cov.: 32 AF XY: 0.832 AC XY: 61881 AN XY: 74388

African (AFR) AF: 0.761 AC: 31553 AN: 41486

American (AMR) AF: 0.822 AC: 12567 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2818 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5150 AN: 5168

South Asian (SAS) AF: 0.940 AC: 4534 AN: 4822

European-Finnish (FIN) AF: 0.878 AC: 9322 AN: 10612

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57621 AN: 67992

Other (OTH) AF: 0.828 AC: 1748 AN: 2110

Alfa AF: 0.839 Hom.: 62366

Bravo AF: 0.823

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		0.47
PromoterAI		-0.046	Neutral
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: rs4787969; hg19: chr16-27561584;