rs1050467693

Variant names:

• chr19-19563529-C-A
• rs1050467693
• NM_025245.3:c.1012G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-19563529-C-A
• chr19-19563529-C-T

Variant summary

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

The NM_025245.3(PBX4):​c.1012G>T​(p.Gly338*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,398,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PBX4 NM_025245.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX4	NM_025245.3	c.1012G>T	p.Gly338*	stop_gained	Exon 7 of 8	ENST00000251203.14	NP_079521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX4	ENST00000251203.14	c.1012G>T	p.Gly338*	stop_gained	Exon 7 of 8	1	NM_025245.3	ENSP00000251203.5
PBX4	ENST00000557978.6	n.*570G>T		non_coding_transcript_exon_variant	Exon 7 of 8	1		ENSP00000453348.1
PBX4	ENST00000557978.6	n.*570G>T		3_prime_UTR_variant	Exon 7 of 8	1		ENSP00000453348.1
PBX4	ENST00000558276.7	n.296G>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1398086 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689596

African (AFR) AF: 0.00 AC: 0 AN: 31626

American (AMR) AF: 0.00 AC: 0 AN: 35678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35860

South Asian (SAS) AF: 0.00 AC: 0 AN: 79174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4922

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078832

Other (OTH) AF: 0.00 AC: 0 AN: 57916

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	33
DANN	Benign	0.92
Eigen	Uncertain	0.30
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.94	D
PhyloP100		3.5
Vest4		0.55
GERP RS		2.2
Mutation Taster		=45/155	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1050467693; hg19: chr19-19674338;