chr1-154945716-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020524.4(PBXIP1):​c.1958G>A​(p.Arg653His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PBXIP1
NM_020524.4 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
PBXIP1NM_020524.4 linkc.1958G>A p.Arg653His missense_variant Exon 10 of 11 ENST00000368463.8 NP_065385.2 Q96AQ6-1
PBXIP1NM_001317734.2 linkc.1871G>A p.Arg624His missense_variant Exon 9 of 10 NP_001304663.1 Q96AQ6-2
PBXIP1NM_001317735.2 linkc.1493G>A p.Arg498His missense_variant Exon 7 of 8 NP_001304664.1 Q96AQ6B4E0K4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PBXIP1ENST00000368463.8 linkc.1958G>A p.Arg653His missense_variant Exon 10 of 11 1 NM_020524.4 ENSP00000357448.3 Q96AQ6-1
PBXIP1ENST00000368465.5 linkc.1871G>A p.Arg624His missense_variant Exon 9 of 10 2 ENSP00000357450.1 Q96AQ6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250744
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135590
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461892
Hom.:
0
Cov.:
34
AF XY:
0.00000825
AC XY:
6
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1958G>A (p.R653H) alteration is located in exon 10 (coding exon 9) of the PBXIP1 gene. This alteration results from a G to A substitution at nucleotide position 1958, causing the arginine (R) at amino acid position 653 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.20
.;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Benign
0.64
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
.;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0050
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.76
MutPred
0.32
.;Gain of catalytic residue at R653 (P = 0.097);
MVP
0.55
MPC
0.82
ClinPred
0.97
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.32

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs758669712; hg19: chr1-154918192; API