16-27618517-C-T

Variant names:

• chr16-27618517-C-T
• rs146695542
• NM_015202.5:c.140+16C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_015202.5(KATNIP):​c.140+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,561,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: KATNIP NM_015202.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.265

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 16-27618517-C-T is Benign according to our data. Variant chr16-27618517-C-T is described in ClinVar as [Benign]. Clinvar id is 1987525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00123 (187/152242) while in subpopulation AFR AF = 0.00388 (161/41538). AF 95% confidence interval is 0.00339. There are 0 homozygotes in GnomAd4. There are 89 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNIP	NM_015202.5	c.140+16C>T		intron_variant	Intron 3 of 27	ENST00000261588.10	NP_056017.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNIP	ENST00000261588.10	c.140+16C>T		intron_variant	Intron 3 of 27	1	NM_015202.5	ENSP00000261588.4
KATNIP	ENST00000568258.5	c.125+16C>T		intron_variant	Intron 2 of 6	3		ENSP00000454884.1
KATNIP	ENST00000618117.1	c.32+16C>T		intron_variant	Intron 1 of 2	5		ENSP00000483214.1
KATNIP	ENST00000565672.5	n.34-10144C>T		intron_variant	Intron 1 of 5	3		ENSP00000455380.1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 187 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00389

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.000366 AC: 92 AN: 251340 AF XY: 0.000309

Gnomad AFR exome AF: 0.00450

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000164 AC: 231 AN: 1409080 Hom.: 0 Cov.: 24 AF XY: 0.000141 AC XY: 99 AN XY: 704312

African (AFR) AF: 0.00374 AC: 121 AN: 32372

American (AMR) AF: 0.000537 AC: 24 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0000776 AC: 2 AN: 25782

East Asian (EAS) AF: 0.00 AC: 0 AN: 39450

South Asian (SAS) AF: 0.0000470 AC: 4 AN: 85124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.000883 AC: 5 AN: 5664

European-Non Finnish (NFE) AF: 0.0000507 AC: 54 AN: 1064090

Other (OTH) AF: 0.000358 AC: 21 AN: 58594

GnomAD4 genome AF: 0.00123 AC: 187 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.00120 AC XY: 89 AN XY: 74434

African (AFR) AF: 0.00388 AC: 161 AN: 41538

American (AMR) AF: 0.000916 AC: 14 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.000323 Hom.: 0

Bravo AF: 0.00150

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 29, 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
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.8
DANN	Benign	0.84
PhyloP100		-0.27
PromoterAI		0.031	Neutral
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs146695542; hg19: chr16-27629838;