chr11-7597584-G-A

Position:

• chr11-7597584-G-A

Variant summary

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

The NM_003621.5(PPFIBP2):​c.397G>A​(p.Glu133Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPFIBP2 NM_003621.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.98

Genes affected

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

LOC105376535 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
PPFIBP2	NM_003621.5	c.397G>A	p.Glu133Lys	missense_variant	5/24	ENST00000299492.9	NP_003612.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIBP2	ENST00000299492.9	c.397G>A	p.Glu133Lys	missense_variant	5/24	1	NM_003621.5	ENSP00000299492.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.397G>A (p.E133K) alteration is located in exon 5 (coding exon 4) of the PPFIBP2 gene. This alteration results from a G to A substitution at nucleotide position 397, causing the glutamic acid (E) at amino acid position 133 to be replaced by a lysine (K). 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	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T;T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	2.9	M;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.81
MutPred		0.29		Gain of ubiquitination at E133 (P = 0.0211);Gain of ubiquitination at E133 (P = 0.0211);.;
MVP		0.69
MPC		0.044
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.46
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-7618815;