rs513287

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRX1	NM_022716.4	c.242-24630G>A		intron_variant		ENST00000239461.11
PRRX1	NM_006902.5	c.242-24630G>A		intron_variant
PRRX1	XM_006711388.4	c.101-24630G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRX1	ENST00000239461.11	c.242-24630G>A		intron_variant		1	NM_022716.4	P1
PRRX1	ENST00000367760.7	c.242-24630G>A		intron_variant		1
PRRX1	ENST00000497230.2	c.242-24630G>A		intron_variant		2
PRRX1	ENST00000553786.1	n.352-24630G>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.510

Alfa AF: 0.483 Hom.: 36674

Bravo AF: 0.498

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.48

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: rs513287; hg19: chr1-170664237;