Genetic Variant KATNIP:c.7+15delG (chr16-27550189-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_015202.5(KATNIP):c.7+15delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,609,084 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 11 hom. )

Consequence

KATNIP
NM_015202.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.90

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 16-27550189-TG-T is Benign according to our data. Variant chr16-27550189-TG-T is described in ClinVar as [Benign]. Clinvar id is 1682047.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00245 (373/152308) while in subpopulation NFE AF = 0.00312 (212/68018). AF 95% confidence interval is 0.00277. There are 3 homozygotes in GnomAd4. There are 203 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNIP	NM_015202.5 link	c.7+15delG		intron_variant	Intron 1 of 27	ENST00000261588.10	NP_056017.4	O60303

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNIP	ENST00000261588.10 link	c.7+13delG		intron_variant	Intron 1 of 27	1	NM_015202.5	ENSP00000261588.4		O60303
KATNIP	ENST00000566023.1 link	n.45+13delG		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

373

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00312

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00277

AC:

690

AN:

249540

AF XY:

0.00277

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000235

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.00319

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00290

AC:

4228

AN:

1456776

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

2103

AN XY:

723680

show subpopulations

Gnomad4 AFR exome

AF:

0.000390

AC:

AN:

33364

Gnomad4 AMR exome

AF:

0.000226

AC:

AN:

44246

Gnomad4 ASJ exome

AF:

0.000346

AC:

AN:

26038

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39544

Gnomad4 SAS exome

AF:

0.00129

AC:

111

AN:

86062

Gnomad4 FIN exome

AF:

0.0112

AC:

595

AN:

53360

Gnomad4 NFE exome

AF:

0.00304

AC:

3371

AN:

1108392

Gnomad4 Remaining exome

AF:

0.00198

AC:

119

AN:

60016

Heterozygous variant carriers

232

464

695

927

1159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00245

AC:

373

AN:

152308

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000577

AC:

0.000577173

AN:

0.000577173

Gnomad4 AMR

AF:

0.000131

AC:

0.000130719

AN:

0.000130719

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000828

AC:

0.000828157

AN:

0.000828157

Gnomad4 FIN

AF:

0.0123

AC:

0.0123492

AN:

0.0123492

Gnomad4 NFE

AF:

0.00312

AC:

0.00311682

AN:

0.00311682

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.00140

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=98/2

polymorphism

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