NM_025245.3:c.857C>A

Variant names:

• chr19-19565001-G-T
• rs550466530
• NM_025245.3:c.857C>A

Variant summary

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

The NM_025245.3(PBX4):​c.857C>A​(p.Thr286Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T286M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PBX4 NM_025245.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88
• Publications: 0 publications found

Genes affected

PBX4 (HGNC:13403): (PBX homeobox 4) This gene encodes a member of the pre-B cell leukemia transcription factor family. These proteins are homeobox proteins that play critical roles in embryonic development and cellular differentiation both as Hox cofactors and through Hox-independent pathways. The encoded protein contains a homeobox DNA-binding domain, but specific functions of the protein have not been determined. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2011]

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=0.18840167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX4	NM_025245.3	c.857C>A	p.Thr286Lys	missense_variant	Exon 6 of 8	ENST00000251203.14	NP_079521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX4	ENST00000251203.14	c.857C>A	p.Thr286Lys	missense_variant	Exon 6 of 8	1	NM_025245.3	ENSP00000251203.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.78
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.9
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Benign	0.27	T
Sift4G	Benign	0.67	T
Polyphen		0.0020	B
Vest4		0.29
MutPred		0.45		Gain of ubiquitination at T286 (P = 0.0048);
MVP		0.91
MPC		0.20
ClinPred		0.31	T
GERP RS		0.0047
Varity_R		0.080
gMVP		0.61
Mutation Taster		=91/9	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: rs550466530; hg19: chr19-19675810;