16-27749769-G-T

Position:

chr16-27749769-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000261588.10(KATNIP):c.2809G>T(p.Asp937Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,610,308 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D937N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 10 hom. )

Consequence

KATNIP
ENST00000261588.10 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.56

Variant links:

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 links:

KATNIP (HGNC:):

KATNIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036624074).

BP6

Variant 16-27749769-G-T is Benign according to our data. Variant chr16-27749769-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 599465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00159 (242/152270) while in subpopulation SAS AF= 0.00644 (31/4816). AF 95% confidence interval is 0.00466. There are 3 homozygotes in gnomad4. There are 135 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNIP	NM_015202.5 linkuse as main transcript	c.2809G>T	p.Asp937Tyr	missense_variant	16/28	ENST00000261588.10	NP_056017.4	O60303

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNIP	ENST00000261588.10 linkuse as main transcript	c.2809G>T	p.Asp937Tyr	missense_variant	16/28	1	NM_015202.5	ENSP00000261588.4		O60303
KATNIP	ENST00000573850.1 linkuse as main transcript	n.914G>T		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

244

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00181

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00255

AC:

632

AN:

247496

Hom.:

AF XY:

0.00298

AC XY:

399

AN XY:

133778

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00490

Gnomad FIN exome

AF:

0.000608

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00207

AC:

3016

AN:

1458038

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

1624

AN XY:

724908

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00149

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00478

Gnomad4 FIN exome

AF:

0.000995

Gnomad4 NFE exome

AF:

0.00176

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00159

AC:

242

AN:

152270

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00644

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00181

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00256

AC:

311

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	KATNIP: BP4, BS2 -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	Jun 30, 2017	BS1, BS2, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, was seen in a healthy adult where full penetrance of the disorder is expected at an early age, and is predicted to be tolerated by multiple functional prediction tools. -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 27, 2021	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.9

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.60

M_CAP

Benign

0.024

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

REVEL

Benign

0.039

Sift

Uncertain

0.016

Sift4G

Uncertain

0.022

Polyphen

0.017

Vest4

0.18

MVP

0.12

MPC

0.56

ClinPred

0.021

GERP RS

2.6

Varity_R

0.083

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over