chr1-170664755-T-C

Variant names:

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

Variant summary

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

The NM_022716.4(PRRX1):​c.241+296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,276 control chromosomes in the GnomAD database, including 50,107 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 0.80 (50107 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRX1	NM_022716.4	c.241+296T>C		intron_variant	Intron 1 of 3	ENST00000239461.11	NP_073207.1
PRRX1	NM_006902.5	c.241+296T>C		intron_variant	Intron 1 of 4		NP_008833.1
PRRX1	XM_006711388.4	c.100+296T>C		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>C		intron_variant	Intron 1 of 3	1	NM_022716.4	ENSP00000239461.6
PRRX1	ENST00000367760.7	c.241+296T>C		intron_variant	Intron 1 of 4	1		ENSP00000356734.3
PRRX1	ENST00000497230.2	c.241+296T>C		intron_variant	Intron 1 of 2	2		ENSP00000450762.1
PRRX1	ENST00000553786.1	n.351+296T>C		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.802 AC: 122096 AN: 152158 Hom.: 50058 Cov.: 35

Gnomad AFR AF: 0.952

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.802 AC: 122198 AN: 152276 Hom.: 50107 Cov.: 35 AF XY: 0.801 AC XY: 59607 AN XY: 74452

African (AFR) AF: 0.952 AC: 39604 AN: 41596

American (AMR) AF: 0.771 AC: 11796 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3045 AN: 3472

East Asian (EAS) AF: 0.408 AC: 2095 AN: 5140

South Asian (SAS) AF: 0.830 AC: 4009 AN: 4832

European-Finnish (FIN) AF: 0.745 AC: 7896 AN: 10604

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51089 AN: 68002

Other (OTH) AF: 0.802 AC: 1696 AN: 2116

Alfa AF: 0.774 Hom.: 180886

Bravo AF: 0.806

Asia WGS AF: 0.622 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.32
PhyloP100		-0.71
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: rs659580; hg19: chr1-170633896;