Variant 1-170719746-GA-GAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_022716.4(PRRX1):c.266_269dupAAAA(p.Arg92fs) variant causes a frameshift change involving the alteration of a 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: 33)

Consequence

PRRX1
NM_022716.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.43

Variant links:

Genes affected

PRRX1 (HGNC:9142): (paired related homeobox 1) The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins localized to the nucleus. The protein functions as a transcription co-activator, enhancing the DNA-binding activity of serum response factor, a protein required for the induction of genes by growth and differentiation factors. The protein regulates muscle creatine kinase, indicating a role in the establishment of diverse mesodermal muscle types. Alternative splicing yields two isoforms that differ in abundance and expression patterns. [provided by RefSeq, Jul 2008]

PRRX1 links:

PRRX1 (HGNC:):

PRRX1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 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 1-170719746-G-GAAAA is Pathogenic according to our data. Variant chr1-170719746-G-GAAAA is described in ClinVar as [Pathogenic]. Clinvar id is 50497.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX1	NM_022716.4 linkuse as main transcript	c.266_269dupAAAA	p.Arg92fs	frameshift_variant	2/4	ENST00000239461.11	NP_073207.1	P54821-1
PRRX1	NM_006902.5 linkuse as main transcript	c.266_269dupAAAA	p.Arg92fs	frameshift_variant	2/5		NP_008833.1	P54821-2
PRRX1	XM_006711388.4 linkuse as main transcript	c.125_128dupAAAA	p.Arg45fs	frameshift_variant	3/5		XP_006711451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRRX1	ENST00000239461.11 linkuse as main transcript	c.266_269dupAAAA	p.Arg92fs	frameshift_variant	2/4	1	NM_022716.4	ENSP00000239461.6	P54821-1
PRRX1	ENST00000367760.7 linkuse as main transcript	c.266_269dupAAAA	p.Arg92fs	frameshift_variant	2/5	1		ENSP00000356734.3	P54821-2
PRRX1	ENST00000497230.2 linkuse as main transcript	c.266_269dupAAAA	p.Arg92fs	frameshift_variant	2/3	2		ENSP00000450762.1	G3V2N3
PRRX1	ENST00000553786.1 linkuse as main transcript	n.376_379dupAAAA		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Agnathia-otocephaly complex

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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