11-7597648-A-T

Variant names:

• chr11-7597648-A-T
• rs538034375
• ENST00000533792:c.-14A>T

Variant summary

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

The ENST00000533792(PPFIBP2):​c.-14A>T variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPFIBP2 ENST00000533792 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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 rank	MANE	Protein	UniProt
PPFIBP2	NM_003621.5	c.461A>T	p.Asn154Ile	missense_variant	Exon 5 of 24	ENST00000299492.9	NP_003612.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIBP2	ENST00000299492.9	c.461A>T	p.Asn154Ile	missense_variant	Exon 5 of 24	1	NM_003621.5	ENSP00000299492.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.029	D;D;D
Sift4G	Benign	0.10	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.56
MutPred		0.37		Loss of disorder (P = 0.0466);Loss of disorder (P = 0.0466);.;
MVP		0.72
MPC		0.11
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.43
gMVP		0.20

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

Other links and lift over

dbSNP: rs538034375; hg19: chr11-7618879;