1-154946065-C-A

Variant names:

• chr1-154946065-C-A
• NM_020524.4:c.1609G>T

Variant summary

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

The NM_020524.4(PBXIP1):​c.1609G>T​(p.Gly537Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G537S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PBXIP1 NM_020524.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0980
• 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: 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=0.14360395).

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.1609G>T	p.Gly537Cys	missense	Exon 10 of 11	NP_065385.2
	PBXIP1	NM_001317734.2		c.1522G>T	p.Gly508Cys	missense	Exon 9 of 10	NP_001304663.1	Q96AQ6-2
	PBXIP1	NM_001317735.2		c.1144G>T	p.Gly382Cys	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.1609G>T	p.Gly537Cys	missense	Exon 10 of 11	ENSP00000357448.3	Q96AQ6-1
	PBXIP1	ENST00000905132.1		c.1717G>T	p.Gly573Cys	missense	Exon 11 of 12	ENSP00000575191.1
	PBXIP1	ENST00000964409.1		c.1717G>T	p.Gly573Cys	missense	Exon 10 of 11	ENSP00000634470.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.098
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.084
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.14		Loss of MoRF binding (P = 0.115)
MVP		0.32
MPC		0.68
ClinPred		0.94	D
GERP RS		2.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.30
gMVP		0.092
Mutation Taster		=98/2	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

hg19: chr1-154918541;