rs708185

Variant names:

• chr12-27536274-C-A
• rs708185
• NM_003622.4:c.-124+11909C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-27536274-C-A
• chr12-27536274-C-G
• chr12-27536274-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003622.4(PPFIBP1):​c.-124+11909C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)
• Consequence: PPFIBP1 NM_003622.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 2 publications found

Genes affected

PPFIBP1 (HGNC:9249): (PPFIA binding protein 1) The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. It has been proposed that liprins are multivalent proteins that form complex structures and act as scaffolds for the recruitment and anchoring of LAR family of tyrosine phosphatases. This protein was found to interact with S100A4, a calcium-binding protein related to tumor invasiveness and metastasis. In vitro experiment demonstrated that the interaction inhibited the phosphorylation of this protein by protein kinase C and protein kinase CK2. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

PPFIBP1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: G2P
• neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003622.4. 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
	PPFIBP1	NM_003622.4	MANE Select	c.-124+11909C>A		intron	N/A	NP_003613.4
	PPFIBP1	NM_177444.3		c.-124+11909C>A		intron	N/A	NP_803193.3	Q86W92-1
	PPFIBP1	NM_001198916.2		c.-124+11909C>A		intron	N/A	NP_001185845.2	Q86W92-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIBP1	ENST00000228425.11	TSL:1 MANE Select	c.-124+11909C>A		intron	N/A	ENSP00000228425.6	Q86W92-2
	PPFIBP1	ENST00000318304.12	TSL:1	c.-124+11909C>A		intron	N/A	ENSP00000314724.8	Q86W92-1
	PPFIBP1	ENST00000542629.5	TSL:1	c.-124+11909C>A		intron	N/A	ENSP00000443442.1	Q86W92-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.10
PhyloP100		-0.25

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: rs708185; hg19: chr12-27689207;