1-170664369-G-T

Position:

chr1-170664369-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022716.4(PRRX1):c.151G>T(p.Ala51Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PRRX1
NM_022716.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.37

Variant links:

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 links:

PRRX1 (HGNC:):

PRRX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11281699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX1	NM_022716.4 linkuse as main transcript	c.151G>T	p.Ala51Ser	missense_variant	1/4	ENST00000239461.11	NP_073207.1	P54821-1
PRRX1	NM_006902.5 linkuse as main transcript	c.151G>T	p.Ala51Ser	missense_variant	1/5		NP_008833.1	P54821-2
PRRX1	XM_006711388.4 linkuse as main transcript	c.10G>T	p.Ala4Ser	missense_variant	2/5		XP_006711451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRRX1	ENST00000239461.11 linkuse as main transcript	c.151G>T	p.Ala51Ser	missense_variant	1/4	1	NM_022716.4	ENSP00000239461.6	P54821-1
PRRX1	ENST00000367760.7 linkuse as main transcript	c.151G>T	p.Ala51Ser	missense_variant	1/5	1		ENSP00000356734.3	P54821-2
PRRX1	ENST00000497230.2 linkuse as main transcript	c.151G>T	p.Ala51Ser	missense_variant	1/3	2		ENSP00000450762.1	G3V2N3
PRRX1	ENST00000553786.1 linkuse as main transcript	n.261G>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249092

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRX1-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 05, 2024

The PRRX1 c.151G>T variant is predicted to result in the amino acid substitution p.Ala51Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.088

.;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.081

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.20

N;N;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.080

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.59

T;T;T

Sift4G

Benign

0.79

T;T;T

Polyphen

0.0070

B;B;.

Vest4

0.053

MutPred

0.28

Gain of phosphorylation at A51 (P = 0.0563);Gain of phosphorylation at A51 (P = 0.0563);Gain of phosphorylation at A51 (P = 0.0563);

MVP

0.48

MPC

0.65

ClinPred

0.86

GERP RS

4.6

Varity_R

0.20

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over