20-21705775-G-A

Variant names:

• chr20-21705775-G-A
• rs980789230
• NM_001257096.2:c.63G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001257096.2(PAX1):​c.63G>A​(p.Ala21Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 1,108,876 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. A21A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: PAX1 NM_001257096.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.313

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]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 20-21705775-G-A is Benign according to our data. Variant chr20-21705775-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1943377.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.313 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2	c.63G>A	p.Ala21Ala	synonymous_variant	Exon 1 of 5	ENST00000613128.5	NP_001244025.1
PAX1	NM_006192.5	c.63G>A	p.Ala21Ala	synonymous_variant	Exon 1 of 5		NP_006183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX1	ENST00000613128.5	c.63G>A	p.Ala21Ala	synonymous_variant	Exon 1 of 5	1	NM_001257096.2	ENSP00000481334.1
PAX1	ENST00000398485.6	c.63G>A	p.Ala21Ala	synonymous_variant	Exon 1 of 5	5		ENSP00000381499.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000631 AC: 7 AN: 1108876 Hom.: 0 Cov.: 31 AF XY: 0.00000756 AC XY: 4 AN XY: 528880

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.000120 AC: 1 AN: 8330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14142

East Asian (EAS) AF: 0.00 AC: 0 AN: 26588

South Asian (SAS) AF: 0.00 AC: 0 AN: 20640

European-Finnish (FIN) AF: 0.0000288 AC: 1 AN: 34768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3078

European-Non Finnish (NFE) AF: 0.00000535 AC: 5 AN: 934290

Other (OTH) AF: 0.00 AC: 0 AN: 44208

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.009110), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 03, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.2
DANN	Benign	0.92
PhyloP100		0.31
PromoterAI		0.0068	Neutral

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

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Other links and lift over

dbSNP: rs980789230; hg19: chr20-21686413;