rs758564832

Variant names:

• chr9-125747544-C-G
• rs758564832
• NM_006195.6:c.91C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-125747544-C-G
• chr9-125747544-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006195.6(PBX3):​c.91C>G​(p.Pro31Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. P31S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PBX3 NM_006195.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

PBX3 (HGNC:8634): (PBX homeobox 3) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in animal organ development; neuron development; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including adult locomotory behavior; dorsal spinal cord development; and regulation of respiratory gaseous exchange by nervous system process. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20712647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX3	NM_006195.6	c.91C>G	p.Pro31Ala	missense_variant	Exon 1 of 9	ENST00000373489.10	NP_006186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX3	ENST00000373489.10	c.91C>G	p.Pro31Ala	missense_variant	Exon 1 of 9	1	NM_006195.6	ENSP00000362588.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454348 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.046	.;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.55	N;.;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.36	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.78	T;T;T
Sift4G	Benign	0.76	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.31
MutPred		0.13		Loss of glycosylation at P31 (P = 0.0238);Loss of glycosylation at P31 (P = 0.0238);Loss of glycosylation at P31 (P = 0.0238);
MVP		0.51
MPC		0.37
ClinPred		0.096	T
GERP RS		2.3
Varity_R		0.095
gMVP		0.16

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: rs758564832; hg19: chr9-128509823;