11-7565628-C-T

Variant names:

• chr11-7565628-C-T
• NM_003621.5:c.140C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003621.5(PPFIBP2):​c.140C>T​(p.Pro47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPFIBP2 NM_003621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14044175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIBP2	NM_003621.5	c.140C>T	p.Pro47Leu	missense_variant	Exon 3 of 24	ENST00000299492.9	NP_003612.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIBP2	ENST00000299492.9	c.140C>T	p.Pro47Leu	missense_variant	Exon 3 of 24	1	NM_003621.5	ENSP00000299492.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.079	T;T;T;T;.
Eigen	Benign	0.065
Eigen_PC	Benign	0.073
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.75	.;T;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	.;.;L;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.6	D;D;N;N;D
REVEL	Benign	0.021
Sift	Benign	0.039	D;D;D;T;D
Sift4G	Uncertain	0.024	D;D;T;T;T
Polyphen		0.0	.;.;B;.;.
Vest4		0.23
MutPred		0.32		Loss of disorder (P = 0.099);Loss of disorder (P = 0.099);Loss of disorder (P = 0.099);Loss of disorder (P = 0.099);Loss of disorder (P = 0.099);
MVP		0.48
MPC		0.029
ClinPred		0.17	T
GERP RS		3.5
Varity_R		0.040
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-7586859; COSMIC: COSV55080464; COSMIC: COSV55080464;