chr16-27550263-G-A

Position:

• chr16-27550263-G-A

Variant summary

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

The ENST00000261588.10(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 ENST00000261588.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.468

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNIP	NM_015202.5	c.7+86G>A		intron_variant		ENST00000261588.10	NP_056017.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNIP	ENST00000261588.10	c.7+86G>A		intron_variant		1	NM_015202.5	ENSP00000261588	P1
KATNIP	ENST00000566023.1	n.45+86G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.827

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.935

Gnomad4 FIN exome AF: 0.881

Gnomad4 NFE exome AF: 0.851

Gnomad4 OTH exome AF: 0.849

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

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.940

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.828

Alfa AF: 0.840 Hom.: 51348

Bravo AF: 0.823

Asia WGS AF: 0.961 AC: 3342 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	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.63

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: rs4787969; hg19: chr16-27561584;