rs1167403013

Variant names:

• chr20-21705781-G-A
• rs1167403013
• NM_001257096.2:c.69G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-21705781-G-A
• chr20-21705781-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001257096.2(PAX1):​c.69G>A​(p.Ala23Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000899 in 1,111,738 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 (★). Synonymous variant affecting the same amino acid position (i.e. A23A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: PAX1 NM_001257096.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.628
• Publications: 0 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-21705781-G-A is Benign according to our data. Variant chr20-21705781-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2908883.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.628 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257096.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX1	NM_001257096.2	MANE Select	c.69G>A	p.Ala23Ala	synonymous	Exon 1 of 5	NP_001244025.1	A0A087WXV5
	PAX1	NM_006192.5		c.69G>A	p.Ala23Ala	synonymous	Exon 1 of 5	NP_006183.2	P15863-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX1	ENST00000613128.5	TSL:1 MANE Select	c.69G>A	p.Ala23Ala	synonymous	Exon 1 of 5	ENSP00000481334.1	A0A087WXV5
	PAX1	ENST00000398485.6	TSL:5	c.69G>A	p.Ala23Ala	synonymous	Exon 1 of 5	ENSP00000381499.2	P15863-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.99e-7 AC: 1 AN: 1111738 Hom.: 0 Cov.: 31 AF XY: 0.00000188 AC XY: 1 AN XY: 530578

African (AFR) AF: 0.00 AC: 0 AN: 22832

American (AMR) AF: 0.000120 AC: 1 AN: 8340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14164

East Asian (EAS) AF: 0.00 AC: 0 AN: 26622

South Asian (SAS) AF: 0.00 AC: 0 AN: 21016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3032

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 936630

Other (OTH) AF: 0.00 AC: 0 AN: 44390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.6
DANN	Benign	0.90
PhyloP100		-0.63
PromoterAI		0.0098	Neutral
Mutation Taster		=100/0	polymorphism

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: rs1167403013; hg19: chr20-21686419;