20-21705767-G-C

Variant names:

• chr20-21705767-G-C
• rs2122130353
• NM_001257096.2:c.55G>C

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.55G>C​(p.Ala19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A19T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAX1 NM_001257096.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=0.24782935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX1	NM_001257096.2	c.55G>C	p.Ala19Pro	missense_variant	Exon 1 of 5	ENST00000613128.5	NP_001244025.1
PAX1	NM_006192.5	c.55G>C	p.Ala19Pro	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.55G>C	p.Ala19Pro	missense_variant	Exon 1 of 5	1	NM_001257096.2	ENSP00000481334.1
PAX1	ENST00000398485.6	c.55G>C	p.Ala19Pro	missense_variant	Exon 1 of 5	5		ENSP00000381499.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.36	T;T
M_CAP	Pathogenic	0.83	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Uncertain	0.033	D
MutationAssessor	Benign	0.90	L;.
PhyloP100		1.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.46	N;.
REVEL	Uncertain	0.32
Sift	Benign	0.079	T;.
Sift4G	Benign	0.40	T;T
Polyphen		0.0010	B;.
Vest4		0.36
MutPred		0.40		Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);
MVP		0.81
MPC		1.7
ClinPred		0.039	T
GERP RS		-1.6
PromoterAI		0.24	Neutral
Varity_R		0.085
gMVP		0.40
Mutation Taster		=88/12	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: rs2122130353; hg19: chr20-21686405;