rs736022

Variant names:

• chr1-170718864-C-T
• rs736022
• NM_022716.4:c.242-862C>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.242-862C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,112 control chromosomes in the GnomAD database, including 4,397 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 0.21 (4397 hom., cov: 32)
• Consequence: PRRX1 NM_022716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRX1	NM_022716.4	c.242-862C>T		intron_variant	Intron 1 of 3	ENST00000239461.11	NP_073207.1
PRRX1	NM_006902.5	c.242-862C>T		intron_variant	Intron 1 of 4		NP_008833.1
PRRX1	XM_006711388.4	c.101-862C>T		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.242-862C>T		intron_variant	Intron 1 of 3	1	NM_022716.4	ENSP00000239461.6
PRRX1	ENST00000367760.7	c.242-862C>T		intron_variant	Intron 1 of 4	1		ENSP00000356734.3
PRRX1	ENST00000497230.2	c.242-862C>T		intron_variant	Intron 1 of 2	2		ENSP00000450762.1
PRRX1	ENST00000553786.1	n.352-862C>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32664 AN: 151994 Hom.: 4394 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.215 AC: 32674 AN: 152112 Hom.: 4397 Cov.: 32 AF XY: 0.220 AC XY: 16383 AN XY: 74332

African (AFR) AF: 0.0665 AC: 2763 AN: 41530

American (AMR) AF: 0.325 AC: 4969 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3472

East Asian (EAS) AF: 0.122 AC: 632 AN: 5174

South Asian (SAS) AF: 0.269 AC: 1295 AN: 4808

European-Finnish (FIN) AF: 0.289 AC: 3049 AN: 10536

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17821 AN: 67984

Other (OTH) AF: 0.253 AC: 533 AN: 2110

Alfa AF: 0.246 Hom.: 1449

Bravo AF: 0.211

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.78
DANN	Benign	0.50
PhyloP100		-0.19
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: rs736022; hg19: chr1-170688005;