rs2122130378

Variant names:

• chr20-21705774-C-A
• rs2122130378
• NM_001257096.2:c.62C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-21705774-C-A
• chr20-21705774-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001257096.2(PAX1):​c.62C>A​(p.Ala21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 1,109,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A21G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: PAX1 NM_001257096.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26557246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2	c.62C>A	p.Ala21Glu	missense_variant	Exon 1 of 5	ENST00000613128.5	NP_001244025.1
PAX1	NM_006192.5	c.62C>A	p.Ala21Glu	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.62C>A	p.Ala21Glu	missense_variant	Exon 1 of 5	1	NM_001257096.2	ENSP00000481334.1
PAX1	ENST00000398485.6	c.62C>A	p.Ala21Glu	missense_variant	Exon 1 of 5	5		ENSP00000381499.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000180 AC: 2 AN: 1109774 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 529392

African (AFR) AF: 0.00 AC: 0 AN: 22872

American (AMR) AF: 0.00 AC: 0 AN: 8352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14176

East Asian (EAS) AF: 0.00 AC: 0 AN: 26680

South Asian (SAS) AF: 0.00 AC: 0 AN: 20594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3096

European-Non Finnish (NFE) AF: 0.00000214 AC: 2 AN: 934802

Other (OTH) AF: 0.00 AC: 0 AN: 44268

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	17
DANN	Uncertain	0.97
DEOGEN2	Benign	0.080	T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.40	T;T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Uncertain	0.072	D
MutationAssessor	Benign	0.46	N;.
PhyloP100		0.34
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.24	N;.
REVEL	Uncertain	0.37
Sift	Uncertain	0.0030	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.64	P;.
Vest4		0.39
MutPred		0.38		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.60
MPC		1.5
ClinPred		0.13	T
GERP RS		1.8
PromoterAI		-0.034	Neutral
Varity_R		0.12
gMVP		0.32
Mutation Taster		=94/6	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

LitVar

Other links and lift over

dbSNP: rs2122130378; hg19: chr20-21686412;