rs750255589

Variant names:

• chr1-154945998-C-T
• rs750255589
• NM_020524.4:c.1676G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_020524.4(PBXIP1):​c.1676G>A​(p.Arg559Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R559W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: PBXIP1 NM_020524.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.90
• Publications: 0 publications found

Genes affected

PBXIP1 (HGNC:21199): (PBX homeobox interacting protein 1) The protein encoded by this gene interacts with the PBX1 homeodomain protein, inhibiting its transcriptional activation potential by preventing its binding to DNA. The encoded protein, which is primarily cytosolic but can shuttle to the nucleus, also can interact with estrogen receptors alpha and beta and promote the proliferation of breast cancer, brain tumors, and lung cancer. Several transcript variants encoding different isoforms have been found for this gene. More variants exist, but their full-length natures have yet to be determined. [provided by RefSeq, Dec 2015]

ENSG00000310191 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008785605).
• BP6: Variant 1-154945998-C-T is Benign according to our data. Variant chr1-154945998-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3209045.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020524.4. 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
	PBXIP1	NM_020524.4	MANE Select	c.1676G>A	p.Arg559Gln	missense	Exon 10 of 11	NP_065385.2
	PBXIP1	NM_001317734.2		c.1589G>A	p.Arg530Gln	missense	Exon 9 of 10	NP_001304663.1	Q96AQ6-2
	PBXIP1	NM_001317735.2		c.1211G>A	p.Arg404Gln	missense	Exon 7 of 8	NP_001304664.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBXIP1	ENST00000368463.8	TSL:1 MANE Select	c.1676G>A	p.Arg559Gln	missense	Exon 10 of 11	ENSP00000357448.3	Q96AQ6-1
	PBXIP1	ENST00000905132.1		c.1784G>A	p.Arg595Gln	missense	Exon 11 of 12	ENSP00000575191.1
	PBXIP1	ENST00000964409.1		c.1784G>A	p.Arg595Gln	missense	Exon 10 of 11	ENSP00000634470.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000191 AC: 48 AN: 251212 AF XY: 0.000133

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461746 Hom.: 0 Cov.: 35 AF XY: 0.0000495 AC XY: 36 AN XY: 727176

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00103 AC: 46 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111912

Other (OTH) AF: 0.000215 AC: 13 AN: 60390

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74360

African (AFR) AF: 0.0000965 AC: 4 AN: 41452

American (AMR) AF: 0.00105 AC: 16 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000928 Hom.: 0

Bravo AF: 0.000427

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.068
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.81
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.39	N
PhyloP100		-2.9
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.016
Sift	Benign	0.61	T
Sift4G	Benign	0.39	T
Polyphen		0.0090	B
Vest4		0.064
MutPred		0.24		Gain of ubiquitination at K554 (P = 0.0249)
MVP		0.19
MPC		0.21
ClinPred		0.039	T
GERP RS		-0.74
Varity_R		0.021
gMVP		0.070
Mutation Taster		=96/4	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: rs750255589; hg19: chr1-154918474;