11-7593181-G-T

Variant names:

• chr11-7593181-G-T
• rs773087319
• NM_003621.5:c.329G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003621.5(PPFIBP2):​c.329G>T​(p.Arg110Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R110H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPFIBP2 NM_003621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 3 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

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.329G>T	p.Arg110Leu	missense	Exon 4 of 24	NP_003612.3	Q8ND30-1
	PPFIBP2	NM_001351853.2		c.329G>T	p.Arg110Leu	missense	Exon 4 of 26	NP_001338782.2
	PPFIBP2	NM_001351854.2		c.329G>T	p.Arg110Leu	missense	Exon 4 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.329G>T	p.Arg110Leu	missense	Exon 4 of 24	ENSP00000299492.4	Q8ND30-1
	PPFIBP2	ENST00000533792.5	TSL:1	c.-146G>T		5_prime_UTR	Exon 2 of 22	ENSP00000436498.1	E9PP16
	PPFIBP2	ENST00000684123.1		c.329G>T	p.Arg110Leu	missense	Exon 4 of 27	ENSP00000507842.1	A0A804HKA2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251464 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		10
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.60		Loss of disorder (P = 0.042)
MVP		0.85
MPC		0.24
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.47
Mutation Taster		=28/72	disease causing

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

dbSNP: rs773087319; hg19: chr11-7614412;