chr11-7597584-G-A

Variant names:

• chr11-7597584-G-A
• NM_003621.5:c.397G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003621.5. 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
	PPFIBP2	NM_003621.5	MANE Select	c.397G>A	p.Glu133Lys	missense	Exon 5 of 24	NP_003612.3	Q8ND30-1
	PPFIBP2	NM_001351853.2		c.397G>A	p.Glu133Lys	missense	Exon 5 of 26	NP_001338782.2
	PPFIBP2	NM_001351854.2		c.397G>A	p.Glu133Lys	missense	Exon 5 of 25	NP_001338783.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP2	ENST00000299492.9	TSL:1 MANE Select	c.397G>A	p.Glu133Lys	missense	Exon 5 of 24	ENSP00000299492.4	Q8ND30-1
	PPFIBP2	ENST00000533792.5	TSL:1	c.-78G>A		5_prime_UTR	Exon 3 of 22	ENSP00000436498.1	E9PP16
	PPFIBP2	ENST00000684123.1		c.397G>A	p.Glu133Lys	missense	Exon 5 of 27	ENSP00000507842.1	A0A804HKA2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	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
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		10
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.29		Gain of ubiquitination at E133 (P = 0.0211)
MVP		0.69
MPC		0.044
ClinPred		0.97	D
GERP RS		5.5
PromoterAI		-0.024	Neutral
Varity_R		0.46
gMVP		0.39
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

hg19: chr11-7618815;