Genetic Variant PAX1:p.Gly25Gly (chr20-21705787-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1

The NM_001257096.2(PAX1):c.75C>T(p.Gly25Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000313 in 1,276,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PAX1
NM_001257096.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.120

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 20-21705787-C-T is Benign according to our data. Variant chr20-21705787-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2884764.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.12 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000159 (24/150976) while in subpopulation AFR AF = 0.000556 (23/41352). AF 95% confidence interval is 0.00038. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2 link	c.75C>T	p.Gly25Gly	synonymous_variant	Exon 1 of 5	ENST00000613128.5	NP_001244025.1	A0A087WXV5
PAX1	NM_006192.5 link	c.75C>T	p.Gly25Gly	synonymous_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.75C>T	p.Gly25Gly	synonymous_variant	Exon 1 of 5	1	NM_001257096.2	ENSP00000481334.1		A0A087WXV5
PAX1	ENST00000398485.6 link	c.75C>T	p.Gly25Gly	synonymous_variant	Exon 1 of 5	5		ENSP00000381499.2		P15863-1

Frequencies

GnomAD3 genomes

AF:

0.000166

AC:

AN:

150870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000582

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

15336

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000142

AC:

AN:

1125126

Hom.:

Cov.:

AF XY:

0.00000926

AC XY:

AN XY:

539846

show subpopulations

African (AFR)

AF:

0.000523

AC:

AN:

22942

American (AMR)

AF:

0.00

AC:

AN:

8418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14298

East Asian (EAS)

AF:

0.00

AC:

AN:

26722

South Asian (SAS)

AF:

0.00

AC:

AN:

24176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3044

European-Non Finnish (NFE)

AF:

0.00000317

AC:

AN:

945586

Other (OTH)

AF:

0.0000222

AC:

AN:

44944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000159

AC:

AN:

150976

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73730

show subpopulations

African (AFR)

AF:

0.000556

AC:

AN:

41352

American (AMR)

AF:

0.0000658

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5074

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67494

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000155

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.9

(source)

DANN

Benign

0.90

PhyloP100

-0.12

PromoterAI

-0.20

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr20-21705787-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over