Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1PP5

The NM_005807.6(PRG4):c.4190_4191delCCinsAG(p.Ser1397*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

PRG4
NM_005807.6 stop_gained

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.69

Publications

1 publications found

Variant links:

Genes affected

PRG4 (HGNC:9364): (proteoglycan 4) The protein encoded by this gene is a large proteoglycan that is synthesized by chondrocytes located at the surface of articular cartilage and by some synovial lining cells. This protein contains both chondroitin sulfate and keratan sulfate glycosaminoglycans. It functions as a boundary lubricant at the cartilage surface and contributes to the elastic absorption and energy dissipation of synovial fluid. Mutations in this gene result in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

PRG4 links:

TPR (HGNC:12017): (translocated promoter region, nuclear basket protein) This gene encodes a large coiled-coil protein that forms intranuclear filaments attached to the inner surface of nuclear pore complexes (NPCs). The protein directly interacts with several components of the NPC. It is required for the nuclear export of mRNAs and some proteins. Oncogenic fusions of the 5' end of this gene with several different kinase genes occur in some neoplasias. [provided by RefSeq, Jul 2008]

TPR Gene-Disease associations (from GenCC):

intellectual developmental disorder, autosomal recessive 79
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

TPR links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 1-186313753-CC-AG is Pathogenic according to our data. Variant chr1-186313753-CC-AG is described in ClinVar as Pathogenic. ClinVar VariationId is 5655.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005807.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRG4	NM_005807.6	MANE Select	c.4190_4191delCCinsAG	p.Ser1397*	stop_gained	N/A	NP_005798.3
TPR	NM_003292.3	MANE Select	c.217_218delGGinsCT		3_prime_UTR	Exon 51 of 51	NP_003283.2
PRG4	NM_001127708.3		c.4067_4068delCCinsAG	p.Ser1356*	stop_gained	N/A	NP_001121180.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRG4	ENST00000445192.7	TSL:5 MANE Select	c.4190_4191delCCinsAG	p.Ser1397*	stop_gained	N/A	ENSP00000399679.3
TPR	ENST00000367478.9	TSL:1 MANE Select	c.217_218delGGinsCT		3_prime_UTR	Exon 51 of 51	ENSP00000356448.3
PRG4	ENST00000367483.8	TSL:5	c.4067_4068delCCinsAG	p.Ser1356*	stop_gained	N/A	ENSP00000356453.4

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.7

Mutation Taster

=0/200

disease causing

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs387906339

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over