rs6047590

Variant names:

• chr20-21712986-T-A
• rs6047590
• NM_001257096.2:c.1283-1485T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257096.2(PAX1):​c.1283-1485T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,136 control chromosomes in the GnomAD database, including 5,116 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (5116 hom., cov: 33)
• Consequence: PAX1 NM_001257096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2	c.1283-1485T>A		intron_variant	Intron 4 of 4	ENST00000613128.5	NP_001244025.1
PAX1	NM_006192.5	c.1283-1495T>A		intron_variant	Intron 4 of 4		NP_006183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX1	ENST00000613128.5	c.1283-1485T>A		intron_variant	Intron 4 of 4	1	NM_001257096.2	ENSP00000481334.1
PAX1	ENST00000398485.6	c.1283-1495T>A		intron_variant	Intron 4 of 4	5		ENSP00000381499.2
PAX1	ENST00000444366.2	c.1211-1485T>A		intron_variant	Intron 3 of 3	2		ENSP00000410355.2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25457 AN: 152018 Hom.: 5081 Cov.: 33

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25537 AN: 152136 Hom.: 5116 Cov.: 33 AF XY: 0.165 AC XY: 12297 AN XY: 74386

African (AFR) AF: 0.480 AC: 19902 AN: 41454

American (AMR) AF: 0.0954 AC: 1460 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3468

East Asian (EAS) AF: 0.153 AC: 789 AN: 5170

South Asian (SAS) AF: 0.0685 AC: 330 AN: 4820

European-Finnish (FIN) AF: 0.0571 AC: 605 AN: 10604

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0288 AC: 1958 AN: 68002

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.108 Hom.: 373

Bravo AF: 0.183

Asia WGS AF: 0.158 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.011
DANN	Benign	0.44
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6047590; hg19: chr20-21693624;