rs17861031

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001257096.2(PAX1):c.555G>A(p.Lys185Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,613,484 control chromosomes in the GnomAD database, including 1,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 565 hom., cov: 32)

Exomes 𝑓: 0.020 ( 942 hom. )

Consequence

PAX1
NM_001257096.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.23

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 20-21706706-G-A is Benign according to our data. Variant chr20-21706706-G-A is described in ClinVar as [Benign]. Clinvar id is 1168083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2 link	c.555G>A	p.Lys185Lys	synonymous_variant	Exon 2 of 5	ENST00000613128.5	NP_001244025.1	A0A087WXV5
PAX1	NM_006192.5 link	c.555G>A	p.Lys185Lys	synonymous_variant	Exon 2 of 5		NP_006183.2	P15863-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAX1	ENST00000613128.5 link	c.555G>A	p.Lys185Lys	synonymous_variant	Exon 2 of 5	1	NM_001257096.2	ENSP00000481334.1	A0A087WXV5
PAX1	ENST00000398485.6 link	c.555G>A	p.Lys185Lys	synonymous_variant	Exon 2 of 5	5		ENSP00000381499.2	P15863-1
PAX1	ENST00000444366.2 link	c.483G>A	p.Lys161Lys	synonymous_variant	Exon 1 of 4	2		ENSP00000410355.2	P15863-2

Frequencies

GnomAD3 genomes

AF:

0.0554

AC:

8434

AN:

152208

Hom.:

565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0254

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0294

AC:

7380

AN:

250862

Hom.:

336

AF XY:

0.0261

AC XY:

3537

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.00566

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.0144

Gnomad FIN exome

AF:

0.00643

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0197

GnomAD4 exome

AF:

0.0201

AC:

29432

AN:

1461158

Hom.:

942

Cov.:

AF XY:

0.0197

AC XY:

14337

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.0183

Gnomad4 ASJ exome

AF:

0.00490

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.0155

Gnomad4 FIN exome

AF:

0.00731

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0243

GnomAD4 genome

AF:

0.0554

AC:

8444

AN:

152326

Hom.:

565

Cov.:

AF XY:

0.0534

AC XY:

3980

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.0255

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0326

Hom.:

123

Bravo

AF:

0.0615

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

EpiCase

AF:

0.0126

EpiControl

AF:

0.0126

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 23, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30572100) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

PAX1-related disorder

Benign:1

Nov 06, 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

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.0

DANN

Benign

0.35

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