Variant 20-21705796-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001257096.2(PAX1):c.84G>C(p.Ala28Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,279,030 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

PAX1
NM_001257096.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.906

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=-0.76).

BP6

Variant 20-21705796-G-C is Benign according to our data. Variant chr20-21705796-G-C is described in ClinVar as [Benign]. Clinvar id is 730360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.906 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00326 (492/150714) while in subpopulation AFR AF= 0.0114 (469/41296). AF 95% confidence interval is 0.0105. There are 5 homozygotes in gnomad4. There are 245 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX1	NM_001257096.2 linkuse as main transcript	c.84G>C	p.Ala28Ala	synonymous_variant	1/5	ENST00000613128.5	NP_001244025.1	A0A087WXV5
PAX1	NM_006192.5 linkuse as main transcript	c.84G>C	p.Ala28Ala	synonymous_variant	1/5		NP_006183.2	P15863-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX1	ENST00000613128.5 linkuse as main transcript	c.84G>C	p.Ala28Ala	synonymous_variant	1/5	1	NM_001257096.2	ENSP00000481334.1		A0A087WXV5
PAX1	ENST00000398485.6 linkuse as main transcript	c.84G>C	p.Ala28Ala	synonymous_variant	1/5	5		ENSP00000381499.2		P15863-1

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

490

AN:

150606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000726

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.0000889

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.000151

AC:

AN:

13228

Hom.:

AF XY:

0.00

AC XY:

AN XY:

6722

show subpopulations

Gnomad AFR exome

AF:

0.00685

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.000339

AC:

382

AN:

1128316

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

159

AN XY:

542724

show subpopulations

Gnomad4 AFR exome

AF:

0.0139

Gnomad4 AMR exome

AF:

0.000237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000755

Gnomad4 SAS exome

AF:

0.0000778

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000316

Gnomad4 OTH exome

AF:

0.00120

GnomAD4 genome

AF:

0.00326

AC:

492

AN:

150714

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

245

AN XY:

73610

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.000725

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000397

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000889

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000487

Hom.:

Bravo

AF:

0.00356

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -

PAX1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 13, 2021

This variant is classified as likely 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

-0.76

CADD

Benign

2.5

DANN

Benign

0.63

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