rs1555531363

Variant names:

• chr17-6620831-TG-T
• rs1555531363
• NM_014804.3:c.1271delC

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_014804.3(KIAA0753):​c.1271delC​(p.Pro424HisfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA0753 NM_014804.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.06
• Publications: 1 publications found

Genes affected

KIAA0753 (HGNC:29110): (KIAA0753) This gene encodes a subunit of a protein complex that regulates ciliogenesis and cilia maintenance. The encoded protein has also been shown to regulate centriolar duplication. Mutations in this gene cause an orofaciodigital syndrome and a form of Joubert syndrome in human patients. [provided by RefSeq, May 2017]

KIAA0753 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome XV

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Franklin by Genoox
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000282936 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-6620831-TG-T is Pathogenic according to our data. Variant chr17-6620831-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 428614.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0753	NM_014804.3	c.1271delC	p.Pro424HisfsTer9	frameshift_variant	Exon 7 of 19	ENST00000361413.8	NP_055619.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0753	ENST00000361413.8	c.1271delC	p.Pro424HisfsTer9	frameshift_variant	Exon 7 of 19	1	NM_014804.3	ENSP00000355250.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Short-rib thoracic dysplasia 21 without polydactyly Pathogenic:1

Oct 07, 2021

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jeune thoracic dystrophy;C0431399:Joubert syndrome Pathogenic:1

Jun 21, 2017

Rare Disease Group, Clinical Genetics, Karolinska Institutet

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=2/198	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1555531363; hg19: chr17-6524151;