Genetic Variant PAX1:p.Arg13Gly (chr20-21705749-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001257096.2(PAX1):c.37A>G(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAX1
NM_001257096.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27833426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 5	ENST00000613128.5	NP_001244025.1	A0A087WXV5
PAX1	NM_006192.5 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 5		NP_006183.2	P15863-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX1	ENST00000613128.5 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 5	1	NM_001257096.2	ENSP00000481334.1		A0A087WXV5
PAX1	ENST00000398485.6 link	c.37A>G	p.Arg13Gly	missense_variant	Exon 1 of 5	5		ENSP00000381499.2		P15863-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1105004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

525246

African (AFR)

AF:

0.00

AC:

AN:

22866

American (AMR)

AF:

0.00

AC:

AN:

8316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14228

East Asian (EAS)

AF:

0.00

AC:

AN:

26570

South Asian (SAS)

AF:

0.00

AC:

AN:

20210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3408

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

929736

Other (OTH)

AF:

0.00

AC:

AN:

44070

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.37A>G (p.R13G) alteration is located in exon 1 (coding exon 1) of the PAX1 gene. This alteration results from a A to G substitution at nucleotide position 37, causing the arginine (R) at amino acid position 13 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.53

T;T

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.28

T;T

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

0.90

L;.

PhyloP100

1.9

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.82

N;.

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;.

Sift4G

Benign

0.14

T;T

Polyphen

0.0

B;.

Vest4

0.20

MutPred

0.41

Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);

MVP

0.69

MPC

2.0

ClinPred

0.48

GERP RS

1.6

PromoterAI

0.036

Neutral

(source)

Varity_R

0.13

gMVP

0.36

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over