rs1553794304

Positions:

• chr3-196707860-G-GT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000409690.5(CEP19):​c.182_183insA​(p.Tyr61Ter) variant causes a stop gained, frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP19 ENST00000409690.5 stop_gained, frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.62

Genes affected

CEP19 (HGNC:28209): (centrosomal protein 19) The protein encoded by this gene localizes to centrosomes and primary cilia and co-localizes with a marker for the mother centriole. This gene resides in a region of human chromosome 3 that is linked to morbid obesity. A homozygous knockout of the orthologous gene in mouse resulted in mice with morbid obesity, hyperphagy, glucose intolerance, and insulin resistance. Mutations in this gene cause morbid obesity and spermatogenic failure (MOSPGF). This gene has a pseudogene on human chromosome 2. [provided by RefSeq, Apr 2014]

PIGX (HGNC:26046): (phosphatidylinositol glycan anchor biosynthesis class X) This gene encodes a type I transmembrane protein in the endoplasmic reticulum (ER). The protein is an essential component of glycosylphosphatidylinositol-mannosyltransferase I, which transfers the first of the four mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis. Studies in rat indicate that the protein is translated from a non-AUG translation initiation site. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-196707860-G-GT is Pathogenic according to our data. Variant chr3-196707860-G-GT is described in ClinVar as [Pathogenic]. Clinvar id is 430642.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP19	NM_032898.5	c.182_183insA	p.Tyr61Ter	stop_gained, frameshift_variant	3/3	ENST00000409690.5	NP_116287.3
CEP19	NM_001379468.1	c.77_78insA	p.Tyr26Ter	stop_gained, frameshift_variant	2/2		NP_001366397.1
CEP19	NM_001379469.1	c.182_183insA	p.Tyr61Ter	stop_gained, frameshift_variant	3/3		NP_001366398.1
CEP19	NM_001379470.1	c.182_183insA	p.Tyr61Ter	stop_gained, frameshift_variant	3/3		NP_001366399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP19	ENST00000409690.5	c.182_183insA	p.Tyr61Ter	stop_gained, frameshift_variant	3/3	1	NM_032898.5	ENSP00000387209	P1
CEP19	ENST00000399942.4	c.77_78insA	p.Tyr26Ter	stop_gained, frameshift_variant	2/2	5		ENSP00000382823
PIGX	ENST00000426755.5	c.-11-8997dup		intron_variant		3		ENSP00000409073

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Bardet-Biedl syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

research

Tolun Lab, Human Genetics Laboratory, Bogazici University

Jul 05, 2017

it is predicted as truncating, but no further studies were performed. -

Computational scores

Source: dbNSFP v4.3

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: rs1553794304; hg19: chr3-196434731;