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. The variant received 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

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

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=0.20712647).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006195.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX3	NM_006195.6	MANE Select	c.91C>G	p.Pro31Ala	missense	Exon 1 of 9	NP_006186.1	P40426-1
	PBX3	NM_001411009.1		c.91C>G	p.Pro31Ala	missense	Exon 1 of 10	NP_001397938.1	Q5JS98
	PBX3	NM_001330782.2		c.91C>G	p.Pro31Ala	missense	Exon 1 of 8	NP_001317711.1	P40426-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX3	ENST00000373489.10	TSL:1 MANE Select	c.91C>G	p.Pro31Ala	missense	Exon 1 of 9	ENSP00000362588.5	P40426-1
	PBX3	ENST00000373482.6	TSL:1	n.91C>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000362581.2	H3BLX0
	PBX3	ENST00000373492.6	TSL:1	n.91C>G		non_coding_transcript_exon	Exon 1 of 7	ENSP00000362591.2	H3BLX0

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

African (AFR) AF: 0.00 AC: 0 AN: 32438

American (AMR) AF: 0.00 AC: 0 AN: 44098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25878

East Asian (EAS) AF: 0.00 AC: 0 AN: 38728

South Asian (SAS) AF: 0.00 AC: 0 AN: 85552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108712

Other (OTH) AF: 0.00 AC: 0 AN: 60052

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.12
Sift	Benign	0.78	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.31
MutPred		0.13		Loss of glycosylation at P31 (P = 0.0238)
MVP		0.51
MPC		0.37
ClinPred		0.096	T
GERP RS		2.3
PromoterAI		-0.15	Neutral
Varity_R		0.095
gMVP		0.16
Mutation Taster		=85/15	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

Other links and lift over

dbSNP: rs758564832; hg19: chr9-128509823;