16-27594376-C-T

Position:

• chr16-27594376-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNIP	NM_015202.5	c.63+20420C>T		intron_variant		ENST00000261588.10	NP_056017.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNIP	ENST00000261588.10	c.63+20420C>T		intron_variant		1	NM_015202.5	ENSP00000261588	P1
KATNIP	ENST00000568258.5	c.50+20420C>T		intron_variant		3		ENSP00000454884
KATNIP	ENST00000565672.5	c.35+20420C>T		intron_variant, NMD_transcript_variant		3		ENSP00000455380

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

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.820

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.72

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: rs4787976; hg19: chr16-27605697;