12-27691297-C-T

Variant names:

• chr12-27691297-C-T
• rs1010096
• NM_003622.4:c.2686-452C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003622.4(PPFIBP1):​c.2686-452C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,512 control chromosomes in the GnomAD database, including 33,129 homozygotes. 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: 𝑓 0.65 (33129 hom., cov: 29)
• Consequence: PPFIBP1 NM_003622.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• Publications: 5 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]

MRPS35-DT (HGNC:55490): (MRPS35 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

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.2686-452C>T		intron	N/A	NP_003613.4
	PPFIBP1	NM_177444.3		c.2704-452C>T		intron	N/A	NP_803193.3	Q86W92-1
	PPFIBP1	NM_001198916.2		c.2611-452C>T		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.2686-452C>T		intron	N/A	ENSP00000228425.6	Q86W92-2
	PPFIBP1	ENST00000318304.12	TSL:1	c.2704-452C>T		intron	N/A	ENSP00000314724.8	Q86W92-1
	PPFIBP1	ENST00000542629.5	TSL:1	c.2611-452C>T		intron	N/A	ENSP00000443442.1	Q86W92-4

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98270 AN: 151394 Hom.: 33124 Cov.: 29

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.649 AC: 98306 AN: 151512 Hom.: 33129 Cov.: 29 AF XY: 0.654 AC XY: 48397 AN XY: 74016

African (AFR) AF: 0.445 AC: 18308 AN: 41158

American (AMR) AF: 0.759 AC: 11567 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2574 AN: 3466

East Asian (EAS) AF: 0.695 AC: 3579 AN: 5150

South Asian (SAS) AF: 0.620 AC: 2962 AN: 4774

European-Finnish (FIN) AF: 0.725 AC: 7595 AN: 10478

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49360 AN: 67940

Other (OTH) AF: 0.700 AC: 1477 AN: 2110

Alfa AF: 0.713 Hom.: 54356

Bravo AF: 0.645

Asia WGS AF: 0.633 AC: 2202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.37
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

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: rs1010096; hg19: chr12-27844230;