rs138641387

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006192.5(PAX1):c.1520C>T(p.Pro507Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,605,734 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 35 hom. )

Consequence

PAX1
NM_006192.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.158

Variant links:

Genes affected

PAX1 (HGNC:8615): (paired box 1) This gene is a member of the paired box (PAX) family of transcription factors. Members of the PAX family typically contain a paired box domain and a paired-type homeodomain. These genes play critical roles during fetal development. This gene plays a role in pattern formation during embryogenesis and may be essential for development of the vertebral column. This gene is silenced by methylation in ovarian and cervical cancers and may be a tumor suppressor gene. Mutations in this gene are also associated with vertebral malformations. [provided by RefSeq, Mar 2012]

PAX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00380221).

BP6

Variant 20-21714718-C-T is Benign according to our data. Variant chr20-21714718-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 377263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.003 (457/152280) while in subpopulation SAS AF= 0.0176 (85/4822). AF 95% confidence interval is 0.0146. There are 1 homozygotes in gnomad4. There are 255 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2 link	c.*156C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000613128.5	NP_001244025.1	A0A087WXV5
PAX1	NM_006192.5 link	c.1520C>T	p.Pro507Leu	missense_variant	Exon 5 of 5		NP_006183.2	P15863-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAX1	ENST00000613128.5 link	c.*156C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001257096.2	ENSP00000481334.1	A0A087WXV5
PAX1	ENST00000398485.6 link	c.1520C>T	p.Pro507Leu	missense_variant	Exon 5 of 5	5		ENSP00000381499.2	P15863-1
PAX1	ENST00000444366.2 link	c.*156C>T		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000410355.2	P15863-2

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

457

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00472

AC:

1137

AN:

240786

Hom.:

AF XY:

0.00553

AC XY:

726

AN XY:

131236

show subpopulations

Gnomad AFR exome

AF:

0.00128

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00411

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.0173

Gnomad FIN exome

AF:

0.00311

Gnomad NFE exome

AF:

0.00374

Gnomad OTH exome

AF:

0.00501

GnomAD4 exome

AF:

0.00386

AC:

5612

AN:

1453454

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

3123

AN XY:

723488

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.00326

Gnomad4 NFE exome

AF:

0.00315

Gnomad4 OTH exome

AF:

0.00453

GnomAD4 genome

AF:

0.00300

AC:

457

AN:

152280

Hom.:

Cov.:

AF XY:

0.00343

AC XY:

255

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0176

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00378

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.00241

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00505

AC:

608

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00502

EpiControl

AF:

0.00439

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 07, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PAX1-related disorder

Benign:1

Jun 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Benign

5.9

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0038

MetaSVM

Uncertain

-0.035

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.44

PROVEAN

Benign

0.070

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.022

Polyphen

0.0

Vest4

0.13

MVP

0.10

MPC

0.24

ClinPred

0.040

GERP RS

-2.1

Varity_R

0.042

gMVP

0.11

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