rs1316065489

Variant names:

• chr11-7565741-A-C
• rs1316065489
• NM_003621.5:c.253A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-7565741-A-C
• chr11-7565741-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003621.5(PPFIBP2):​c.253A>C​(p.Ile85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,876 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: 0.0000027 (0 hom.)
• Consequence: PPFIBP2 NM_003621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053892583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIBP2	NM_003621.5	c.253A>C	p.Ile85Leu	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.253A>C	p.Ile85Leu	missense_variant	Exon 3 of 24	1	NM_003621.5	ENSP00000299492.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.78
DEOGEN2	Benign	0.0082	T;T;T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.62	.;T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.054	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.38	.;.;N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.33	N;N;N;N
REVEL	Benign	0.049
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.86	T;T;T;T
Polyphen		0.0010	.;.;B;.
Vest4		0.35
MutPred		0.48		Loss of catalytic residue at I85 (P = 0.0432);Loss of catalytic residue at I85 (P = 0.0432);Loss of catalytic residue at I85 (P = 0.0432);Loss of catalytic residue at I85 (P = 0.0432);
MVP		0.23
MPC		0.028
ClinPred		0.10	T
GERP RS		3.3
Varity_R		0.034
gMVP		0.21

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: rs1316065489; hg19: chr11-7586972;