chr1-170664428-C-T

Position:

• chr1-170664428-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_022716.4(PRRX1):​c.210C>T​(p.Leu70Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000549 in 1,608,154 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (3 hom.)
• Consequence: PRRX1 NM_022716.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.70

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 1-170664428-C-T is Benign according to our data. Variant chr1-170664428-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX1	NM_022716.4	c.210C>T	p.Leu70Leu	synonymous_variant	1/4	ENST00000239461.11	NP_073207.1
PRRX1	NM_006902.5	c.210C>T	p.Leu70Leu	synonymous_variant	1/5		NP_008833.1
PRRX1	XM_006711388.4	c.69C>T	p.Leu23Leu	synonymous_variant	2/5		XP_006711451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRX1	ENST00000239461.11	c.210C>T	p.Leu70Leu	synonymous_variant	1/4	1	NM_022716.4	ENSP00000239461.6
PRRX1	ENST00000367760.7	c.210C>T	p.Leu70Leu	synonymous_variant	1/5	1		ENSP00000356734.3
PRRX1	ENST00000497230.2	c.210C>T	p.Leu70Leu	synonymous_variant	1/3	2		ENSP00000450762.1
PRRX1	ENST00000553786.1	n.320C>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000587 AC: 137 AN: 233564 Hom.: 0 AF XY: 0.000740 AC XY: 94 AN XY: 127000

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00155

Gnomad FIN exome AF: 0.000201

Gnomad NFE exome AF: 0.000719

Gnomad OTH exome AF: 0.000523

GnomAD4 exome AF: 0.000563 AC: 820 AN: 1455834 Hom.: 3 Cov.: 33 AF XY: 0.000619 AC XY: 448 AN XY: 723632

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00141

Gnomad4 FIN exome AF: 0.000133

Gnomad4 NFE exome AF: 0.000564

Gnomad4 OTH exome AF: 0.000550

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74482

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000508 Hom.: 0

Bravo AF: 0.000363

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.96

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: rs372174969; hg19: chr1-170633569;