rs368123079

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001257096.2(PAX1):c.1282+12A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,509,864 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 21 hom. )

Consequence

PAX1
NM_001257096.2 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -3.28

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 20-21709456-A-C is Benign according to our data. Variant chr20-21709456-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 445455.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00313 (477/152272) while in subpopulation NFE AF= 0.00559 (380/68006). AF 95% confidence interval is 0.00512. There are 1 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2 link	c.1282+12A>C		intron_variant	Intron 4 of 4	ENST00000613128.5	NP_001244025.1	A0A087WXV5
PAX1	NM_006192.5 link	c.1282+12A>C		intron_variant	Intron 4 of 4		NP_006183.2	P15863-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAX1	ENST00000613128.5 link	c.1282+12A>C	intron_variant	Intron 4 of 4	1	NM_001257096.2	ENSP00000481334.1	A0A087WXV5
PAX1	ENST00000398485.6 link	c.1282+12A>C	intron_variant	Intron 4 of 4	5		ENSP00000381499.2	P15863-1
PAX1	ENST00000444366.2 link	c.1210+12A>C	intron_variant	Intron 3 of 3	2		ENSP00000410355.2	P15863-2
PAX1	ENST00000485038.1 link	n.*179A>C	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

477

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00559

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00261

AC:

308

AN:

118064

Hom.:

AF XY:

0.00253

AC XY:

161

AN XY:

63684

show subpopulations

Gnomad AFR exome

AF:

0.000560

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.000167

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000862

Gnomad NFE exome

AF:

0.00574

Gnomad OTH exome

AF:

0.00222

GnomAD4 exome

AF:

0.00521

AC:

7068

AN:

1357592

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

3417

AN XY:

668084

show subpopulations

Gnomad4 AFR exome

AF:

0.000848

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.0000860

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.00631

Gnomad4 OTH exome

AF:

0.00375

GnomAD4 genome

AF:

0.00313

AC:

477

AN:

152272

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00559

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.00288

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PAX1: BS2 -

Jun 01, 2017

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 30, 2022

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1282+12A>C variant in PAX1 is classified as likely benign because it is not located within the splice consensus sequence and computational splice prediction tools do not predict an impact on splicing. It has also been identified in 0.558% (339/60720) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and in one individual with Klippel-Feil syndrome (McGaughran 2003 PMID: 12774041). ACMG/AMP Criteria applied: BP4, BP7. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.025

DANN

Benign

0.59

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