rs659580

Variant names:

• chr1-170664755-T-A
• rs659580
• NM_022716.4:c.241+296T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-170664755-T-A
• chr1-170664755-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022716.4(PRRX1):​c.241+296T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: PRRX1 NM_022716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 22 publications found

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 Gene-Disease associations (from GenCC):

• craniosynostosis

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• agnathia-otocephaly complex

  Inheritance: AD, Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• multiple congenital anomalies/dysmorphic syndrome-intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRX1	NM_022716.4	c.241+296T>A		intron_variant	Intron 1 of 3	ENST00000239461.11	NP_073207.1
PRRX1	NM_006902.5	c.241+296T>A		intron_variant	Intron 1 of 4		NP_008833.1
PRRX1	XM_006711388.4	c.100+296T>A		intron_variant	Intron 2 of 4		XP_006711451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRX1	ENST00000239461.11	c.241+296T>A		intron_variant	Intron 1 of 3	1	NM_022716.4	ENSP00000239461.6
PRRX1	ENST00000367760.7	c.241+296T>A		intron_variant	Intron 1 of 4	1		ENSP00000356734.3
PRRX1	ENST00000497230.2	c.241+296T>A		intron_variant	Intron 1 of 2	2		ENSP00000450762.1
PRRX1	ENST00000553786.1	n.351+296T>A		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 35

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

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		-0.71

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: rs659580; hg19: chr1-170633896;