Genetic Variant PAX1:p.Gly18Val (chr20-21705765-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001257096.2(PAX1):c.53G>T(p.Gly18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000899 in 1,112,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G18R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

PAX1
NM_001257096.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.517

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09201977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2 link	c.53G>T	p.Gly18Val	missense_variant	Exon 1 of 5	ENST00000613128.5	NP_001244025.1	A0A087WXV5
PAX1	NM_006192.5 link	c.53G>T	p.Gly18Val	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.53G>T	p.Gly18Val	missense_variant	Exon 1 of 5	1	NM_001257096.2	ENSP00000481334.1		A0A087WXV5
PAX1	ENST00000398485.6 link	c.53G>T	p.Gly18Val	missense_variant	Exon 1 of 5	5		ENSP00000381499.2		P15863-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.99e-7

AC:

AN:

1112012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

530308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22926

American (AMR)

AF:

0.000119

AC:

AN:

8388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14264

East Asian (EAS)

AF:

0.00

AC:

AN:

26806

South Asian (SAS)

AF:

0.00

AC:

AN:

20666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3170

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

935934

Other (OTH)

AF:

0.00

AC:

AN:

44424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

7.5

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.44

T;T

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.092

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.0

N;.

PhyloP100

-0.52

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.17

N;.

REVEL

Benign

0.24

Sift

Benign

0.15

T;.

Sift4G

Benign

0.14

T;T

Polyphen

0.0010

B;.

Vest4

0.15

MutPred

0.31

Loss of disorder (P = 0.0408);Loss of disorder (P = 0.0408);

MVP

0.56

MPC

1.7

ClinPred

0.046

GERP RS

-0.45

PromoterAI

0.089

Neutral

(source)

Varity_R

0.061

gMVP

0.16

Mutation Taster

=94/6

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

Computational scores

Splicing

Publications

Other links and lift over