NM_003625.5:c.406-3629C>T

Variant names:

• chr12-81449349-G-A
• rs12426725
• NM_003625.5:c.406-3629C>T

Variant summary

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

The NM_003625.5(PPFIA2):​c.406-3629C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,970 control chromosomes in the GnomAD database, including 2,917 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 0.19 (2917 hom., cov: 32)
• Consequence: PPFIA2 NM_003625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 3 publications found

Genes affected

PPFIA2 (HGNC:9246): (PTPRF interacting protein alpha 2) 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 has been shown to bind the calcium/calmodulin-dependent serine protein kinase (MAGUK family) protein (also known as CASK) and proposed to regulate higher-order brain functions in mammals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

PPFIA2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

PPFIA2-AS2 (HGNC:58195):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003625.5. 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
	PPFIA2	NM_003625.5	MANE Select	c.406-3629C>T		intron	N/A	NP_003616.2
	PPFIA2	NM_001220476.2		c.406-3629C>T		intron	N/A	NP_001207405.1	O75334-3
	PPFIA2	NM_001220473.3		c.406-3629C>T		intron	N/A	NP_001207402.1	G3V200

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIA2	ENST00000549396.6	TSL:1 MANE Select	c.406-3629C>T		intron	N/A	ENSP00000450337.1	O75334-1
	PPFIA2	ENST00000548586.5	TSL:1	c.406-3629C>T		intron	N/A	ENSP00000449338.1	O75334-3
	PPFIA2	ENST00000550584.6	TSL:1	c.406-3629C>T		intron	N/A	ENSP00000449558.2	G3V200

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28221 AN: 151852 Hom.: 2907 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.0853

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.186 AC: 28260 AN: 151970 Hom.: 2917 Cov.: 32 AF XY: 0.187 AC XY: 13920 AN XY: 74286

African (AFR) AF: 0.270 AC: 11169 AN: 41418

American (AMR) AF: 0.161 AC: 2465 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.0445 AC: 230 AN: 5170

South Asian (SAS) AF: 0.0860 AC: 413 AN: 4804

European-Finnish (FIN) AF: 0.197 AC: 2074 AN: 10546

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10508 AN: 67980

Other (OTH) AF: 0.196 AC: 415 AN: 2112

Alfa AF: 0.163 Hom.: 5736

Bravo AF: 0.188

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.20
PhyloP100		-1.1
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: rs12426725; hg19: chr12-81843128;