NM_001257096.2:c.53G>A

Variant names:

• chr20-21705765-G-A
• rs1984955809
• NM_001257096.2:c.53G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001257096.2(PAX1):​c.53G>A​(p.Gly18Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,112,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G18R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: PAX1 NM_001257096.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.517

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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093686104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2	c.53G>A	p.Gly18Glu	missense_variant	Exon 1 of 5	ENST00000613128.5	NP_001244025.1
PAX1	NM_006192.5	c.53G>A	p.Gly18Glu	missense_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.53G>A	p.Gly18Glu	missense_variant	Exon 1 of 5	1	NM_001257096.2	ENSP00000481334.1
PAX1	ENST00000398485.6	c.53G>A	p.Gly18Glu	missense_variant	Exon 1 of 5	5		ENSP00000381499.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000450 AC: 5 AN: 1112012 Hom.: 0 Cov.: 31 AF XY: 0.00000377 AC XY: 2 AN XY: 530308

African (AFR) AF: 0.00 AC: 0 AN: 22926

American (AMR) AF: 0.00 AC: 0 AN: 8388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14264

East Asian (EAS) AF: 0.00 AC: 0 AN: 26806

South Asian (SAS) AF: 0.00 AC: 0 AN: 20666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3170

European-Non Finnish (NFE) AF: 0.00000534 AC: 5 AN: 935934

Other (OTH) AF: 0.00 AC: 0 AN: 44424

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.0035	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	7.7
DANN	Benign	0.92
DEOGEN2	Benign	0.082	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.42	T;T
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.094	T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		-0.52
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.28	N;.
REVEL	Benign	0.22
Sift	Benign	0.10	T;.
Sift4G	Benign	0.24	T;T
Polyphen		0.040	B;.
Vest4		0.17
MutPred		0.34		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.42
MPC		1.7
ClinPred		0.058	T
GERP RS		-0.45
PromoterAI		0.17	Neutral
Varity_R		0.085
gMVP		0.12
Mutation Taster		=93/7	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

Publications

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Other links and lift over

dbSNP: rs1984955809; hg19: chr20-21686403;