rs17861031

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

otofaciocervical syndrome 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

PAX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.0294

AC:

7380

AN:

250862

AF XY:

0.0261

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 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

African (AFR)

AF:

0.149

AC:

4980

AN:

33480

American (AMR)

AF:

0.0183

AC:

819

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

128

AN:

26134

East Asian (EAS)

AF:

0.143

AC:

5660

AN:

39700

South Asian (SAS)

AF:

0.0155

AC:

1340

AN:

86258

European-Finnish (FIN)

AF:

0.00731

AC:

385

AN:

52698

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0131

AC:

14563

AN:

1112002

Other (OTH)

AF:

0.0243

AC:

1468

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2089

4178

6268

8357

10446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

706

1412

2118

2824

3530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0554

AC:

8444

AN:

152326

Hom.:

565

Cov.:

AF XY:

0.0534

AC XY:

3980

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.150

AC:

6254

AN:

41576

American (AMR)

AF:

0.0255

AC:

390

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.123

AC:

633

AN:

5162

South Asian (SAS)

AF:

0.0147

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00584

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0134

AC:

911

AN:

68036

Other (OTH)

AF:

0.0416

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

390

780

1169

1559

1949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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) -

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

(source)

DANN

Benign

0.35

PhyloP100

1.2

PromoterAI

0.015

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over