rs513287

Variant names:

• chr1-170695096-G-A
• rs513287
• NM_022716.4:c.242-24630G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-170695096-G-A
• chr1-170695096-G-C
• chr1-170695096-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022716.4(PRRX1):​c.242-24630G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,932 control chromosomes in the GnomAD database, including 19,008 homozygotes. 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: 𝑓 0.50 (19008 hom., cov: 32)
• Consequence: PRRX1 NM_022716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022716.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRX1	NM_022716.4	MANE Select	c.242-24630G>A		intron	N/A	NP_073207.1
	PRRX1	NM_006902.5		c.242-24630G>A		intron	N/A	NP_008833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRX1	ENST00000239461.11	TSL:1 MANE Select	c.242-24630G>A		intron	N/A	ENSP00000239461.6
	PRRX1	ENST00000367760.7	TSL:1	c.242-24630G>A		intron	N/A	ENSP00000356734.3
	PRRX1	ENST00000497230.2	TSL:2	c.242-24630G>A		intron	N/A	ENSP00000450762.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75644 AN: 151814 Hom.: 18986 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.498 AC: 75696 AN: 151932 Hom.: 19008 Cov.: 32 AF XY: 0.509 AC XY: 37825 AN XY: 74246

African (AFR) AF: 0.462 AC: 19133 AN: 41436

American (AMR) AF: 0.597 AC: 9102 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1924 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2700 AN: 5150

South Asian (SAS) AF: 0.594 AC: 2859 AN: 4814

European-Finnish (FIN) AF: 0.570 AC: 6017 AN: 10550

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32127 AN: 67952

Other (OTH) AF: 0.510 AC: 1078 AN: 2112

Alfa AF: 0.482 Hom.: 76786

Bravo AF: 0.498

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.48
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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: rs513287; hg19: chr1-170664237;